Opportunities for Regulatory Authorities to Assess Animal-Based Measures at the Slaughterhouse Using Sensor Technology and Artificial Intelligence: A Review.

Animal-based measures (ABMs) are the preferred way to assess animal welfare. However, manual scoring of ABMs is very time-consuming during the meat inspection. Automatic scoring by using sensor technology and artificial intelligence (AI) may bring a solution. Based on review papers an overview was made of ABMs recorded at the slaughterhouse for poultry, pigs and cattle and applications of sensor technology to measure the identified ABMs. Also, relevant legislation and work instructions of the Dutch Regulatory Authority (RA) were scanned on applied ABMs. Applications of sensor technology in a research setting, on farm or at the slaughterhouse were reported for 10 of the 37 ABMs identified for poultry, 4 of 32 for cattle and 13 of 41 for pigs. Several applications are related to aspects of meat inspection. However, by European law meat inspection must be performed by an official veterinarian, although there are exceptions for the post mortem inspection of poultry. The examples in this study show that there are opportunities for using sensor technology by the RA to support the inspection and to give more insight into animal welfare risks. The lack of external validation for multiple commercially available systems is a point of attention.

White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the animal sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

BACKGROUND: The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions to link the surveillance of antimicrobial usage (AMU) and antimicrobial resistance (AMR) with antimicrobial stewardship (AMS) activities in four different settings. This White Paper focuses on the veterinary setting and embraces the One Health approach. METHODS: A review of the literature was carried out addressing research questions in three areas: AMS leadership and accountability; AMU surveillance and AMS; and AMR surveillance and AMS. Consensus on target actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine and public health, from 18 countries. RESULTS/DISCUSSION: Forty-six target actions were developed and qualified as essential or desirable. Essential actions included the setup of AMS teams in all veterinary settings, building government-supported AMS programmes and following specific requirements on the production, collection and communication of AMU and AMR data. Activities of AMS teams should be tailored to the local situation and capacities, and be linked to local or national surveillance systems and infection control programmes. Several research priorities were also identified, such as the need to develop more clinical breakpoints in veterinary medicine. CONCLUSIONS: This White Paper offers a practical tool to veterinary practitioners and policy makers to improve AMS in the One Health approach, thanks to surveillance data generated in the veterinary setting. This work may also be useful to medical doctors wishing to better understand the specificities of the veterinary setting and facilitate cross-sectoral collaborations.

Social media posts and online search behaviour as early-warning system for MRSA outbreaks.

Background: Despite many preventive measures, outbreaks with multi-drug resistant micro-organisms (MDROs) still occur. Moreover, current alert systems from healthcare organizations have shortcomings due to delayed or incomplete notifications, which may amplify the spread of MDROs by introducing infected patients into a new healthcare setting and institutions. Additional sources of information about upcoming and current outbreaks, may help to prevent further spread of MDROs.The study objective was to evaluate whether methicillin-resistant Staphylococcus aureus (MRSA) outbreaks could be detected via social media posts or online search behaviour; if so, this might allow earlier detection than the official notifications by healthcare organizations. Methods: We conducted an exploratory study in which we compared information about MRSA outbreaks in the Netherlands derived from two online sources, Coosto for Social Media, and Google Trends for search behaviour, to the mandatory Dutch outbreak notification system (SO-ZI/AMR). The latter provides information on MDRO outbreaks including the date of the outbreak, micro-organism involved, the region/location, and the type of health care organization. Results: During the research period of 15 months (455 days), 49 notifications of outbreaks were recorded in SO-ZI/AMR. For Coosto, the number of unique potential outbreaks was 37 and for Google Trends 24. The use of social media and online search behaviour missed many of the hospital outbreaks that were reported to SO-ZI/AMR, but detected additional outbreaks in long-term care facilities. Conclusions: Despite several limitations, using information from social media and online search behaviour allows rapid identification of potential MRSA outbreaks, especially in healthcare settings with a low notification compliance. When combined in an automated system with real-time updates, this approach might increase early discovery and subsequent implementation of preventive measures.

Surveillance for control of antimicrobial resistance.

Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions, infection control policies, and antimicrobial development. In Europe, although the European Antimicrobial Resistance Surveillance Network provides annual reports on monitored resistant bacteria, national surveillance efforts are still fragmented and heterogeneous, and have substantial structural problems and issues with laboratory data. Most incidence and prevalence data cannot be linked with relevant epidemiological, clinical, or outcome data. Genetic typing, to establish whether trends of antimicrobial resistance are caused by spread of resistant strains or by transfer of resistance determinants among different strains and species, is not routinely done. Furthermore, laboratory-based surveillance using only clinical samples is not likely to be useful as an early warning system for emerging pathogens and resistance mechanisms. Insufficient coordination of surveillance systems of human antimicrobial resistance with animal surveillance systems is even more concerning. Because results from food surveillance are considered commercially sensitive, they are rarely released publicly by regulators. Inaccurate or incomplete surveillance data delay a translational approach to the threat of antimicrobial resistance and inhibit the identification of relevant target microorganisms and populations for research and the revitalisation of dormant drug-discovery programmes. High-quality, comprehensive, and real-time surveillance data are essential to reduce the burden of antimicrobial resistance. Improvement of national antimicrobial resistance surveillance systems and better alignment between human and veterinary surveillance systems in Europe must become a scientific and political priority, coordinated with international stakeholders within a global approach to reduce the burden of antimicrobial resistance.

Age-dependent differences in the pathogenesis of bovine respiratory syncytial virus infections related to the development of natural immunocompetence.

The severity of respiratory syncytial virus (RSV) infections appears to differ with age in both humans and bovines. A primary RSV infection in naïve infants and in young calves runs a more severe course when they are 1-6 months old than in their first month of life. The relative lack of clinical signs in the first month of age may be due to high levels of maternally derived neutralizing antibodies or low exposure to infectious virus. This study examined whether age-dependent differences in the pathogenesis of bovine RSV (bRSV) between neonatal and young calves may be due to differences in age-dependent immunocompetence. To study the effect of age and immune parameters on bRSV disease in neonatal and young calves, neonatal (1-day-old) calves without maternally derived antibodies were infected experimentally with bRSV and the severity of disease and immune responses were evaluated in comparison with disease in similar 6-week-old infected calves. Neonatal calves had more extensive virus replication and lung consolidation, but lower pro-inflammatory [in particular tumour necrosis factor alpha (TNF-α)] responses, specific humoral immune responses, lung neutrophilic infiltration and clinical signs of disease than 6-week-old calves. The lack of correlation between virus replication and clinical signs suggests an important role of pro-inflammatory cytokines, in particular TNF-α, in the disease. The capacity to produce pro-inflammatory TNF-α appeared to increase with age, and may explain the age-dependent differences in RSV pathogenesis.

Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and calves. Bovine RSV (bRSV) is a natural pathogen for cattle, and bRSV infection in calves shares many features with the human infection. Thus, bRSV infection in cattle provides the ideal setting to evaluate the safety and efficacy of novel RSV vaccine strategies. Here, we have evaluated the efficacy and safety of modified vaccinia virus Ankara (rMVA)-based vaccine candidates, expressing the bovine RSV-F protein, either or not in combination with the G protein, in colostrums-deprived SPF calves born by caesarean section. Vaccination induced bRSV-specific IgG and CD8 T cell responses. Importantly, no IgE responses were detected. After bRSV challenge, rMVA vaccinated calves experienced less severe symptoms of lower respiratory tract disease compared to the mock-immunized control group. Immunized animals showed reduced pulmonary virus loads, and no eosinophilic infiltration or enhanced respiratory distress. In conclusion, candidate rMVA/bRSV vaccines induced protective and safe immune responses in calves.

Kinetics of antiviral CD8 T cell responses during primary and post-vaccination secondary bovine respiratory syncytial virus infection.

We have measured antiviral CD8 T cells responses in bovine respiratory syncytial virus (bRSV) infected calves that had been immunized with either formalin-inactivated (FI) or live-attenuated (L) bRSV, with evidence of immunopathology following challenge of calves vaccinated with FI-bRSV. In all cases, bRSV infection induced potent pulmonary CD8 T cell responses. The kinetics of the post-challenge response in L-bRSV immunized animals was accelerated compared to the FI-bRSV and PBS groups, suggesting that only the L-bRSV vaccine, and not the FI-bRSV vaccine, had primed memory T cells. The differences between primary and post-vaccination secondary infection were very minor, in terms of the proliferation status of pulmonary CD8 T cells. Functional IFN-gamma+ CD8 responses were slightly higher in the FI-bRSV vaccinated animals. Furthermore, the existence of strong IFN-gamma+ CD8 responses in FI-bRSV vaccinated animals after challenge suggests (i) that these IFN-gamma+ responses in FI-bRSV immunized animals do not protect against immunopathology, and (ii) that Th-2 biased responses during bRSV challenge after vaccination with FI-bRSV have a limited impact on the CD8 responses in the bronchoalveolar lavage fluid. Thus, several response patterns (Th-l/Th-2) seem to co-exist during bRSV infection.

Vaccine-induced immunopathology during bovine respiratory syncytial virus infection: exploring the parameters of pathogenesis.

The bovine and human respiratory syncytial viruses cause severe lower respiratory tract infections. Effective vaccines against the respiratory syncytial viruses have been lacking since vaccine failures in the 1960s and 1970s. In this report, we describe a bovine respiratory syncytial virus (bRSV) challenge model in which both classical bRSV respiratory infection and vaccine-enhanced immune pathology were reproduced. The classical, formalin-inactivated (FI) bRSV vaccine that has been associated with vaccine failure was efficient in inducing high antibody titers and reducing viral loads but also primed calves for a far more serious enhanced respiratory disease after a bRSV challenge, thereby mimicking the enhanced clinical situation in FI human RSV (hRSV)-immunized and hRSV-infected infants in the 1960s. We show that immunization with FI-bRSV mainly primes a Th2-like inflammatory response that is characterized by a significant eosinophilic influx in the bronchial alveolar lung fluid and lung tissues and high levels of immunoglobulin E serum antibodies. The current model may be useful in the evaluation of new bRSV candidate vaccines for potency and safety.

A solid-phase blocking ELISA for detection of type O foot-and-mouth disease virus antibodies suitable for mass serology.

A simple solid-phase blocking ELISA for the detection of antibodies directed against type O foot-and-mouth disease virus (FMDV) was developed. The ELISA was validated using field sera collected from cattle, pigs and sheep originating from FMDV infected and non-infected Dutch farms, reference sera obtained from the World Reference Laboratory for foot-and-mouth disease at the Institute for Animal Health, Pirbright Laboratory, UK and sera from experimentally infected animals. Testing 2664 sera collected from non-infected cattle, pigs and sheep resulted in a specificity of 96%. A sensitivity relative to the virus neutralisation test (VNT) of >99% was achieved when testing 148 positive cattle, goat and sheep sera collected from FMDV-infected Dutch farms. All international reference sera scored consistently correct. The ELISA also correctly scored 398 of 409 positive experimentally derived sera. The sensitivity and specificity of this monoclonal antibody-based ELISA for detection of type O FMDV antibodies is sufficient for use as a screening ELISA. During the 2001 epidemic in the Netherlands, 8000 serum samples per day were regularly tested in this ELISA. The samples scoring positive were then tested by neutralisation for confirmation thus making optimum use of the neutralisation testing capacity.