A framework for the design, implementation, and evaluation of output-based surveillance systems against zoonotic threats.

Output-based standards set a prescribed target to be achieved by a surveillance system, but they leave the selection of surveillance parameters, such as test type and population to be sampled, to the responsible party in the surveillance area. This allows proportionate legislative surveillance specifications to be imposed over a range of unique geographies. This flexibility makes output-based standards useful in the context of zoonotic threat surveillance, particularly where animal pathogens act as risk indicators for human health or where multiple surveillance streams cover human, animal, and food safety sectors. Yet, these systems are also heavily reliant on the appropriate choice of surveillance options to fit the disease context and the constraints of the organization implementing the surveillance system. Here we describe a framework to assist with designing, implementing, and evaluating output-based surveillance systems showing the effectiveness of a diverse range of activities through a case study example. Despite not all activities being relevant to practitioners in every context, this framework aims to provide a useful toolbox to encourage holistic and stakeholder-focused approaches to the establishment and maintenance of productive output-based surveillance systems.

A review of qualitative risk assessment in animal health: Suggestions for best practice.

Qualitative risk assessment (QRA) can provide decision support in line with the requirement for an objective, unbiased assessment of disease risk according to the Agreement on the Application of Sanitary and Phytosanitary Measures of the World Trade Organization. However, in order for a QRA to be objective and consistently applied it is necessary to standardize the approach as much as possible. This review considers how QRAs have historically been used for the benefit of animal health, what problems have been encountered during their progression, and considers best practice for their future use. Four main elements were identified as having been the subject of some proposed standard methodology: (i) the description of risk levels, (ii) combining probabilities, (iii) accounting for trade volume and time period, and (iv) uncertainty. These elements were addressed in different ways but were highlighted as being fundamental to improving the robustness in estimating the risk and conveying the results to the risk manager with minimal ambiguity. In line with this, several tools have been developed which attempt to use mathematical reasoning to incorporate uncertainty and improve the objectivity of the qualitative framework. This represents an important advance in animal health QRA. Overall, animal health QRAs have established their usefulness by providing a tool for rapid risk estimation which can be used to identify important chains of events and critical control points along risk pathways and inform risk management programmes as to whether or not the risk exceeds a decision-making threshold above which action should be taken. Ensuring a robust objective methodology is used and that the reasons for differences in results, such as assumptions and uncertainty are clearly described to the customer with minimal ambiguity is essential to maintain confidence in the QRA process. However, further work needs to be done to determine if one objective uniform methodology should be developed and considered best practice. To this end, a set of best practice guidelines presenting the optimal way to conduct a QRA and regulated by bodies such as the World Organization for Animal Health or the European Food Safety Authority would be beneficial.

A review of cleaning and disinfection guidelines and recommendations following an outbreak of classical scrapie.

Classical scrapie is a prion disease of small ruminants, the infectious agent of which has been shown to be extremely persistent in the environment. Cleaning and disinfection (C&D) after a scrapie outbreak is currently recommended by many governments' veterinary advisors and implemented in most farms affected. Yet, the effectiveness of these procedures remains unclear. The aim of this study was to review existing literature and guidelines regarding farm C&D protocols following classical scrapie outbreaks and assess their effectiveness and the challenges that translation of policy and legislative requirements present at a practical level. A review of the literature was conducted to identify the on-farm C&D protocols used following outbreaks of scrapie, assess those materials with high risk for persistence of the scrapie agent on farms, and review the existing evidence of the effectiveness of recommended C&D protocols. An expert workshop was also organised in Great Britain (GB) to assess: the decision-making process used when implementing C&D protocols on GB farms, the experts' perceptions on the effectiveness of these protocols and changes needed, and their views on potential recommendations for policy and research. Outputs of the literature review revealed that the current recommended protocol for C&D [1 h treatment with sodium hypochlorite containing 20,000 ppm free chlorine or 2 M sodium hydroxide (NaOH)] is based on laboratory experiments. Only four field farm experiments have been conducted, indicating a lack of data on effectiveness of C&D protocols on farms by the re-occurrence of scrapie infection post re-stocking. Recommendations related to the control of outdoor environment, which are difficult and expensive to implement, vary between countries. The expert workshop concluded that there are no practical, cost-effective C&D alternatives to be considered at this time, with control therefore based on C&D only in combination with additional time restrictions on re-stocking and replacement with non-susceptible livestock or more genetically resistant types, where available. Participants agreed that C&D should still be completed on scrapie affected farms, as it is considered to be "good disease practice" and likely to reduce the levels of the prion protein. Participants felt that any additional protocols developed should not be "too prescriptive" (should not be written down in specific policies) because of significant variation in farm types, farm equipment and installations. Under this scenario, control of classical scrapie on farms should be designed with a level of C&D in combination with re-stocking temporal ban and replacement with livestock of limited susceptibility.

Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom.

In 2018 prion disease was detected in camels at an abattoir in Algeria for the first time. The emergence of prion disease in this species made it prudent to assess the probability of entry of the pathogen into the United Kingdom (UK) from this region. Potentially contaminated products were identified as evidenced by other prion diseases. The aggregated probability of entry of the pathogen was estimated as very high and high for legal milk and cheese imports respectively and very high, high and high for illegal meat, milk and cheese products respectively. This aggregated probability represents a qualitative assessment of the probability of one or more entry events per year into the UK; it gives no indication of the number of entry events per year. The uncertainty associated with these estimates was high due to the unknown variation in prevalence of infection in camels and an uncertain number and type of illegal products entering the UK. Potential public health implications of this pathogen are unknown although there is currently no evidence of zoonotic transmission of prion diseases other than bovine spongiform encephalopathy to humans.

Estimating the impact on food and edible materials of changing scrapie control measures: The scrapie control model.

Multiple controls established during the bovine spongiform encephalopathy (BSE) epidemic were not solely applied to BSE in cattle, but were implemented for scrapie in sheep and goats due to concerns over the occurrence of BSE in sheep. In the absence of BSE in sheep being observed, control measures for prion diseases are now being evaluated to ensure they remain proportionate to risk. This risk assessment, aims to estimate, by use of stochastic simulation, the impact of reducing controls for Specified Risk Materials (SRM) from sheep at abattoir. Three scenarios have been included: 1) current list of SRM; 2) brain and spinal cord of adult sheep; and 3) the brain of adult sheep. Results indicate the total amount of infectivity passing through British abattoirs is highest for atypical scrapie with nearly 3,500,000 Ovine Oral (OO) ID50 per year. The majority of this infectivity enters Category 1 waste for incineration, with only 13,000 OO ID50 per year within edible products. Under Scenario 2, an additional 4000 OO ID50 per year would be classified as edible products from the lifting of restrictions on the distal ileum of adult sheep. However, if SRM removal was limited to brain, an additional 110,000 OO ID50 per year would be permitted into edible products with the lifting of restrictions on the spinal cord of adult sheep. For classical scrapie, there is a mean estimate of infectivity of 30,000 OO ID50 per year at abattoir. This is lower than for atypical scrapie due to the lower occurrence of this disease in Great Britain. However, more infectivity is destined to reach the food chain as the disease is peripherally distributed in the carcase. The highest contributor to the total amount of infectivity consumed per year is the intestines (duodenum and jejunum). If SRM removal is limited to the brain and spinal cord of sheep over 12 months of age, there is an approximate mean increase from 19,000 to 21,000 OO ID50 per year diverted to edible products. If the SRM list is restricted to brain only, this increases to over 23,000 OO ID50 per year. For the potential of sheep-BSE, there is a very low estimate of 29 OO ID50 per year in total from carcases entering abattoir, due to the potential very rare occurrence of this disease. Given changes in SRM regulations there is a change of an additional 4 OO ID50 per year being diverted to edible products.

Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States.

This paper presents a quantitative assessment model for the risk of entry of zoonotic bat-borne viruses into the European Union (EU). The model considers four routes of introduction: human travel, legal trade of products, live animal imports and illegal import of bushmeat and was applied to five virus outbreak scenarios. Two scenarios were considered for Zaire ebolavirus (wEBOV, cEBOV) and other scenarios for Hendra virus, Marburg virus (MARV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The use of the same framework and generic data sources for all EU Member States (MS) allows for a relative comparison of the probability of virus introduction and of the importance of the routes of introduction among MSs. According to the model wEBOV posed the highest risk of an introduction event within the EU, followed by MARV and MERS-CoV. However, the main route of introduction differed, with wEBOV and MERS-CoV most likely through human travel and MARV through legal trade of foodstuffs. The relative risks to EU MSs as entry points also varied between outbreak scenarios, highlighting the heterogeneity in global trade and travel to the EU MSs. The model has the capability to allow for a continual updating of the risk estimate using new data as, and when, it becomes available. The model provides an horizon scanning tool for use when available data are limited and, therefore, the absolute risk estimates often have high uncertainty. Sensitivity analysis suggested virus prevalence in bats has a large influence on the results; a 90% reduction in prevalence reduced the risk of introduction considerably and resulted in the relative ranking of MARV falling below that for MERS-CoV, due to this parameter disproportionately affecting the risk of introduction from the trade route over human travel.

A Generic Quantitative Risk Assessment Framework for the Entry of Bat-Borne Zoonotic Viruses into the European Union.

Bat-borne viruses have been linked to a number of zoonotic diseases; in 2014 there have been human cases of Nipah virus (NiV) in Bangladesh and Ebola virus in West and Central Africa. Here we describe a model designed to provide initial quantitative predictions of the risk of entry of such viruses to European Union (EU) Member States (MSs) through four routes: human travel, legal trade (e.g. fruit and animal products), live animal movements and illegal importation of bushmeat. The model utilises available datasets to assess the movement via these routes between individual countries of the world and EU MSs. These data are combined with virus specific data to assess the relative risk of entry between EU MSs. As a case study, the model was parameterised for NiV. Scenario analyses showed that the selection of exporting countries with NiV and potentially contaminated trade products were essential to the accuracy of all model outputs. Uncertainty analyses of other model parameters identified that the model expected number of years to an introduction event within the EU was highly susceptible to the prevalence of NiV in bats. The relative rankings of the MSs and routes, however, were more robust. The UK, the Netherlands and Germany were consistently the most likely points of entry and the ranking of most MSs varied by no more than three places (maximum variation five places). Legal trade was consistently the most likely route of entry, only falling below human travel when the estimate of the prevalence of NiV in bats was particularly low. Any model-based calculation is dependent on the data available to feed into the model and there are distinct gaps in our knowledge, particularly in regard to various pathogen/virus as well as host/bat characteristics. However, the strengths of this model lie in the provision of relative comparisons of risk among routes and MSs. The potential for expansion of the model to include other routes and viruses and the possibility of rapid parameterisation demonstrates its potential for use in an outbreak situation.

Potential for introduction of bat-borne zoonotic viruses into the EU: a review.

Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU.