Helene Wahlström

EMA and EFSA Joint Scientific Opinion on measures to reduce the need to use antimicrobial agents in animal husbandry in the European Union, and the resulting impacts on food safety (RONAFA)

Abstract EFSA and EMA have jointly reviewed measures taken in the EU to reduce the need for and use of antimicrobials in food‐producing animals, and the resultant impacts on antimicrobial resistance (AMR). Reduction strategies have been implemented successfully in some Member States. Such strategies include national reduction targets, benchmarking of antimicrobial use, controls on prescribing and restrictions on use of specific critically important antimicrobials, together with improvements to animal husbandry and disease prevention and control measures. Due to the multiplicity of factors contributing to AMR, the impact of any single measure is difficult to quantify, although there is evidence of an association between reduction in antimicrobial use and reduced AMR. To minimise antimicrobial use, a multifaceted integrated approach should be implemented, adapted to local circumstances. Recommended options (non‐prioritised) include: development of national strategies; harmonised systems for monitoring antimicrobial use and AMR development; establishing national targets for antimicrobial use reduction; use of on‐farm health plans; increasing the responsibility of veterinarians for antimicrobial prescribing; training, education and raising public awareness; increasing the availability of rapid and reliable diagnostics; improving husbandry and management procedures for disease prevention and control; rethinking livestock production systems to reduce inherent disease risk. A limited number of studies provide robust evidence of alternatives to antimicrobials that positively influence health parameters. Possible alternatives include probiotics and prebiotics, competitive exclusion, bacteriophages, immunomodulators, organic acids and teat sealants. Development of a legislative framework that permits the use of specific products as alternatives should be considered. Further research to evaluate the potential of alternative farming systems on reducing AMR is also recommended. Animals suffering from bacterial infections should only be treated with antimicrobials based on veterinary diagnosis and prescription. Options should be reviewed to phase out most preventive use of antimicrobials and to reduce and refine metaphylaxis by applying recognised alternative measures.

Update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA 6: suitability of taxonomic units notified to EFSA until March 2017

Abstract The qualified presumption of safety (QPS) concept was developed to provide a harmonised generic pre‐evaluation to support safety risk assessments of biological agents performed by EFSAs scientific Panels. The identity, body of knowledge, safety concerns and antimicrobial resistance of valid taxonomic units were assessed. Safety concerns identified for a taxonomic unit are, where possible and reasonable in number, reflected as ‘qualifications’ which should be assessed at the strain level by the EFSAs scientific Panels. No new information was found that would change the previously recommended QPS taxonomic units and their qualifications. Between the end of September 2016 and March 2017, the QPS notification list was updated with 87 applications for market authorisation. From these, 32 biological agents already had a QPS status, and 37 were not included in the evaluation as they are filamentous fungi or enterococci. Streptomyces species (Streptomyces cinnamonensis, Streptomyces mobaraensis and Streptomyces violaceoruber), Bacillus circulans (three notifications) and Escherichia coli (seven notifications) were re‐confirmed not suitable for QPS. Streptomyces rubiginosus and Streptomyces netropsis, not evaluated within the previous mandate, were also not recommended for QPS. Streptomyces spp. and E. coli will be excluded from further QPS evaluations within the current QPS mandate. Hyphomicrobium denitrificans, which has never been evaluated before, was not recommended for the QPS list and for Pseudomonas amyloderamosa, the QPS assessment was not applicable because it is not a validated species. Lactobacillus animalis was a new taxonomic unit recommended to have the QPS status.

First identification of Echinococcus multilocularis in rodent intermediate hosts in Sweden.

Echinococcus multilocularis is a zoonotic tapeworm with a sylvatic lifecycle and an expanding range in Europe. Monitoring efforts following its first identification in 2011 in Sweden have focused on the parasites definitive host, the red fox (Vulpes vulpes). However, identifying rodent intermediate hosts is important to recognize opportunities for parasite transmission. During 2013–2015, livers from a total of 1566 rodents from four regions in Sweden were examined for E. multilocularis metacestode lesions. Species identity of suspect parasite lesions was confirmed by PCR and sequencing. E. multilocularis positive lesions >6 mm in diameter were also examined histologically. One Microtus agrestis out of 187 (0.5%, 95%CI: 0–2.9%), 8/439 (1.8%, 95%CI: 0.8–3.6%) Arvicola amphibius, 0/655 (0%, 95%CI: 0–0.6%) Myodes glareolus, and 0/285 (0%, 95%CI: 0–1.3%) Apodemus spp. contained E. multilocularis metacestode lesions. Presence of protoscoleces was confirmed in the infected M. agrestis and in three of eight infected A. amphibius. Six of the nine positive rodents were captured from the same field. This is the first report of E. multilocularis in intermediate hosts in Sweden. The cluster of positive rodents in one field shows that local parasite prevalence can be high in Sweden despite overall low national prevalence in foxes (<0.1%). The presence of protoscoleces in infected M. agrestis and A. amphibius indicate these species can serve as competent intermediate hosts in Sweden. However, their relative importance for E. multilocularis transmission in the Swedish environment is not yet possible to assess. In contrast, the negative findings in all M. glareolus and Apodemus spp. suggest that these species are of no importance.

Economic Effects of Introducing Alternative Salmonella Control Strategies in Sweden

The objective of the study was to analyse the economic effects of introducing alternative Salmonella control strategies in Sweden. Current control strategies in Denmark and the Netherlands were used as benchmarks. The true number of human Salmonella cases was estimated by reconstructing the reporting pyramids for the various scenarios. Costs were calculated for expected changes in human morbidity (Salmonella and two of its sequelae), for differences in the control programmes and for changes in cattle morbidity. The net effects (benefits minus costs) were negative in all scenarios (€ −5 to −105 million), implying that it would not be cost-effective to introduce alternative control strategies in Sweden. This result was mainly due to an expected increase in the incidence of Salmonella in humans (6035–57108 reported and unreported new cases/year), with expected additional costs of € 5–55 million. Other increased costs were due to expected higher incidences of sequelae (€ 3–49 million) and a higher cattle morbidity (€ 4–8 million). Benefits in terms of lower control costs amounted to € 4–7 million.

Genetic resistance to transmissible spongiform encephalopathies (TSE) in goats

Abstract Breeding programmes to promote resistance to classical scrapie, similar to those for sheep in existing transmissible spongiform encephalopathies (TSE) regulations, have not been established in goats. The European Commission requested a scientific opinion from EFSA on the current knowledge of genetic resistance to TSE in goats. An evaluation tool, which considers both the weight of evidence and strength of resistance to classical scrapie of alleles in the goat PRNP gene, was developed and applied to nine selected alleles of interest. Using the tool, the quality and certainty of the field and experimental data are considered robust enough to conclude that the K222, D146 and S146 alleles both confer genetic resistance against classical scrapie strains known to occur naturally in the EU goat population, with which they have been challenged both experimentally and under field conditions. The weight of evidence for K222 is greater than that currently available for the D146 and S146 alleles and for the ARR allele in sheep in 2001. Breeding for resistance can be an effective tool for controlling classical scrapie in goats and it could be an option available to member states, both at herd and population levels. There is insufficient evidence to assess the impact of K222, D146 and S146 alleles on susceptibility to atypical scrapie and bovine spongiform encephalopathy (BSE), or on health and production traits. These alleles are heterogeneously distributed across the EU Member States and goat breeds, but often at low frequencies (< 10%). Given these low frequencies, high selection pressure may have an adverse effect on genetic diversity so any breeding for resistance programmes should be developed at Member States, rather than EU level and their impact monitored, with particular attention to the potential for any negative impact in rare or small population breeds.

Detection of Echinococcus multilocularis by MC-PCR: evaluation of diagnostic sensitivity and specificity without gold standard

Introduction A semi-automated magnetic capture probe-based DNA extraction and real-time PCR method (MC-PCR), allowing for a more efficient large-scale surveillance of Echinococcus multilocularis occurrence, has been developed. The test sensitivity has previously been evaluated using the sedimentation and counting technique (SCT) as a gold standard. However, as the sensitivity of the SCT is not 1, test characteristics of the MC-PCR was also evaluated using latent class analysis, a methodology not requiring a gold standard. Materials and methods Test results, MC-PCR and SCT, from a previous evaluation of the MC-PCR using 177 foxes shot in the spring (n=108) and autumn 2012 (n=69) in high prevalence areas in Switzerland were used. Latent class analysis was used to estimate the test characteristics of the MC-PCR. Although it is not the primary aim of this study, estimates of the test characteristics of the SCT were also obtained. Results and discussion This study showed that the sensitivity of the MC-PCR was 0.88 [95% posterior credible interval (PCI) 0.80–0.93], which was not significantly different than the SCT, 0.83 (95% PCI 0.76–0.88), which is currently considered as the gold standard. The specificity of both tests was high, 0.98 (95% PCI 0.94–0.99) for the MC-PCR and 0.99 (95% PCI 0.99–1) for the SCT. In a previous study, using fox scats from a low prevalence area, the specificity of the MC-PCR was higher, 0.999% (95% PCI 0.997–1). One reason for the lower estimate of the specificity in this study could be that the MC-PCR detects DNA from infected but non-infectious rodents eaten by foxes. When using MC-PCR in low prevalence areas or areas free from the parasite, a positive result in the MC-PCR should be regarded as a true positive. Conclusion The sensitivity of the MC-PCR (0.88) was comparable to the sensitivity of SCT (0.83).

Comparison of whole genome sequencing typing results and epidemiological contact information from outbreaks of Salmonella Dublin in Swedish cattle herds

Background Whole genome sequencing (WGS) is becoming a routine tool for infectious disease outbreak investigations. The Swedish situation provides an excellent opportunity to test the usefulness of WGS for investigation of outbreaks with Salmonella Dublin (S. Dublin) as epidemiological investigations are always performed when Salmonella is detected in livestock production, and index isolates from all detected herds are stored and therefore available for analysis. This study was performed to evaluate WGS as a tool in forward and backward tracings from herds infected with S. Dublin. Material and methods In this study, 28 isolates from 26 cattle herds were analysed and the WGS results were compared with results from the epidemiological investigations, for example, information on contacts between herds. The isolates originated from herds in three different outbreaks separated geographically and to some extent also in time, and from the only region in Sweden where S. Dublin is endemic (Öland). Results The WGS results of isolates from the three non-endemic regions were reliably separated from each other and from the endemic isolates. Within the outbreaks, herds with known epidemiological contacts generally showed smaller differences between isolates as compared to when there were no known epidemiological contacts. Conclusion The results indicate that WGS can provide valuable supplemental information in S. Dublin outbreak investigations. The resolution of the WGS was sufficient to distinguish isolates from the different outbreaks and provided additional information to the investigations within an outbreak.

Chronic wasting disease (CWD) in cervids

Abstract In April and May of 2016, Norway confirmed two cases of chronic wasting disease (CWD) in a wild reindeer and a wild moose, respectively. In the light of this emerging issue, the European Commission requested EFSA to recommend surveillance activities and, if necessary, additional animal health risk‐based measures to prevent the introduction of the disease and the spread into/within the EU, specifically Estonia, Finland, Iceland, Latvia, Lithuania, Norway, Poland and Sweden, and considering seven wild, semidomesticated and farmed cervid species (Eurasian tundra reindeer, Finnish (Eurasian) forest reindeer, moose, roe deer, white‐tailed deer, red deer and fallow deer). It was also asked to assess any new evidence on possible public health risks related to CWD. A 3‐year surveillance system is proposed, differing for farmed and wild or semidomesticated cervids, with a two‐stage sampling programme at the farm/geographically based population unit level (random sampling) and individual level (convenience sampling targeting high‐risk animals). The current derogations of Commission Implementing Decision (EU) 2016/1918 present a risk of introduction of CWD into the EU. Measures to prevent the spread of CWD within the EU are dependent upon the assumption that the disease is already present; this is currently unknown. The measures listed are intended to contain (limit the geographic extent of a focus) and/or to control (actively stabilise/reduce infection rates in an affected herd or population) the disease where it occurs. With regard to the zoonotic potential, the human species barrier for CWD prions does not appear to be absolute. These prions are present in the skeletal muscle and other edible tissues, so humans may consume infected material in enzootic areas. Epidemiological investigations carried out to date make no association between the occurrence of sporadic Creutzfeldt–Jakob disease in humans and exposure to CWD prions.

A questionnaire study of associations between potential risk factors and salmonella status in Swedish dairy herds

In this study associations between potential risk factors and salmonella status in Swedish dairy herds were investigated. A case-control study design was used, including existing as well as new cases. Herds were assigned a salmonella status on the basis of antibody analysis of bulk milk samples. Information on potential risk factors was collected from registry data and from farmers via a questionnaire. Univariable and multivariable logistic regression analyses were used to investigate associations between salmonella status and potential risk factors. In addition, multivariate analysis with Additive Bayesian Network (ABN) modelling was performed to improve understanding of the complex relationship between all the variables. Because of the difficulty in identifying associations between potential risk factors and infections with low prevalence and a large regional variation, exposure of potential risk factors in the high-prevalence region (Öland) were compared to exposure in other regions in Sweden. In total 483 of 996 (48%) farmers responded to the questionnaire, 69 herds had test-positive bulk milk samples. The strongest association with salmonella status was presence of salmonella test-positive herds <5 km (OR 4.3, 95% CI 2.0-9.4). Associations with salmonella status were also seen between feeding calves residue milk only (OR 2.4, 95% CI 1.2-4.6), certified organic herds (OR 2.5, 95% CI 1.2-4.9) and frequently seeing signs of rodents (OR 0.4, 95% CI 0.13-0.97). The ABN model showed associations between Öland and four of the variables: salmonella status, presence of test-positive herds <5km, shared pastures and providing protective clothing for visitors. The latter is probably a reflection of increased disease awareness in Öland. The ABN model showed associations between herd size and housing as well as several management procedures. This provides an explanation why herd size frequently has been identified as a risk factor for salmonella by other studies. The study confirms the importance of local transmission routes for salmonella, but does not identify specific components in this local spread. Therefore, it supports the use of a broad biosecurity approach in the prevention of salmonella. In Öland, some potential risk factors are more common than in other parts of Sweden. Theoretically these could contribute to the spread of salmonella, but this was not confirmed in the present study. The study also highlights the difficulty in identifying associations between potential risk factors and infections with low prevalence and large regional variation.

Hazard analysis approaches for certain small retail establishments in view of the application of their food safety management systems

Abstract Under current European hygiene legislation, food businesses are obliged to develop and implement food safety management systems (FSMS) including prerequisite programme (PRP) activities and hazard analysis and critical control point principles. This requirement is especially challenging for small food retail establishments, where a lack of expertise and other resources may limit the development and implementation of effective FSMS. In this opinion, a simplified approach to food safety management is developed and presented based on a fundamental understanding of processing stages (flow diagram) and the activities contributing to increased occurrence of the hazards (biological, chemical (including allergens) or physical) that may occur. The need to understand and apply hazard or risk ranking within the hazard analysis is removed and control is achieved using PRP activities as recently described in the European Commission Notice 2016/C278, but with the addition of a PRP activity covering ‘product information and customer awareness’. Where required, critical limits, monitoring and record keeping are also included. Examples of the simplified approach are presented for five types of retail establishments: butcher, grocery, bakery, fish and ice cream shop.