Maria Stokstad

Background Bovine respiratory disease (BRD) is a major cause of morbidity, mortality, impaired welfare, production loss, and antimicrobial use in cattle. These European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) guidelines provide evidence-based recommendations for antimicrobial and non-steroidal anti-inflammatory drug (NSAID) use in cattle with acute, undifferentiated BRD, balancing animal-level outcomes with antimicrobial stewardship. Methods Recommendations were developed using the GRADE approach and Evidence-to-Decision frameworks, following ENOVAT procedures and RIGHT reporting guidance. Evidence came from two prespecified systematic reviews and meta-analyses of randomized controlled trials evaluating individual treatment of clinical BRD: one comparing antimicrobial classes head-to-head and one evaluating NSAIDs as adjunctive treatment or monotherapy. Metaphylaxis and prophylaxis were excluded. Certainty of evidence was assessed with GRADE. Panel judgments incorporated stakeholder-derived thresholds for clinically meaningful differences in short-term therapeutic failure, defined as need for antimicrobial re-treatment, and a merged stewardship perspective based on WHO antimicrobial importance and EMA AMEG categories. Results Across antimicrobial comparisons, no class showed a clinically meaningful advantage in reducing short-term re-treatment sufficient to override stewardship considerations. The panel conditionally suggests penicillin G, oxytetracycline, or florfenicol as first-line empirical treatment, guided by local susceptibility data, herd treatment history, product authorization, withdrawal periods, and suspicion of Mycoplasmopsis bovis infection. Macrolides are conditionally suggested as second-line treatment, preferably guided by culture and susceptibility testing or documented treatment failure. Fluoroquinolones are recommended against as primary or secondary treatment, except in exceptional, justified circumstances consistent with regulations. Adding NSAIDs to antimicrobials did not meaningfully reduce antimicrobial re-treatment; the panel recommends against NSAID use for this specific purpose. Evidence was insufficient to recommend for or against NSAIDs for welfare-related outcomes or as antimicrobial substitutes. Conclusions These guidelines prioritize effective BRD treatment while reducing unnecessary use of higher-priority antimicrobials. Local adoption or adaptation using GRADE-ADOLOPMENT is recommended.

The bovine respiratory disease (BRD) complex is a major health and welfare challenge in the cattle industry worldwide, with substantial economic and antimicrobial resistance implications. Pasteurella multocida (PM) is a key bacterial agent of BRD; however, knowledge gaps remain regarding its transmission dynamics, genomic diversity and virulence-associated gene repertoire in cattle. In this cross-sectional study, we used population genomics to characterize PM isolates circulating in Norwegian calves and compare them with global bovine PM lineages. By integrating genomics with epidemiological and clinical data from both healthy and BRD-affected animals across different herd production systems, we identified associations between PM genotypes, herd-level factors and disease status. Fattening herds harboured greater PM diversity than dairy herds, and herd-specific population structures were common, with limited evidence of recent inter-herd transmission. Sequence type (ST) 173 was strongly associated with clinical signs of respiratory disease and exhibited a distinct genomic profile, including genes linked to iron acquisition and quorum sensing. A possible tropism for the lower respiratory tract was also observed for this ST. In contrast, ST79 was more prevalent among healthy animals and appeared to act predominantly as a commensal. Nasal swabs often, but not always, reflected the PM strain present in the lungs, highlighting both the utility and limitations of non-invasive diagnostics. Collectively, these findings demonstrate that herd management and bacterial genetic diversity play key roles in BRD epidemiology. Accordingly, targeted control strategies should account for the heterogeneity and pathogenic potential of circulating PM strains.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as ancillary therapy for bovine respiratory disease (BRD) alongside antimicrobials, and interest in NSAID monotherapy has grown amid antimicrobial stewardship and welfare concerns. We evaluated the clinical effectiveness of NSAIDs for BRD as adjunctive or sole therapy. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in cattle with naturally occurring BRD. Databases searched were MEDLINE (Ovid), Embase (Ovid), CAB Abstracts (Ovid), Biological Abstracts (Ovid), Web of Science Core Collection, and Scopus (search: 22 Apr 2024; update: 12 Sep 2025). Primary outcomes were short-term treatment failure (need for re-treatment); secondary outcomes included relapse, mortality, adverse events, and performance where available. Random-effects pairwise meta-analyses estimated risk ratios (RRs) with 95% CIs. Risk of bias was assessed with a modified RoB 2.0 tool; certainty of evidence was appraised using GRADE. Registration/protocol: this review extends a prior ENOVAT BRD protocol; no separate registration was created. Funding: COST Action CA18217. Results Seventeen RCTs (22 comparisons; 4,909 animals) compared NSAID+antimicrobial versus antimicrobial alone. Adding an NSAID did not reduce re-treatment (RR 0.94, 95% CI 0.84–1.05; I 2 = 0%; moderate certainty). Subgroup (same vs different antimicrobial) and sensitivity analyses (handling of multi-arm trials; follow-up restricted to ≤14 or ≤ 10 days; risk-of-bias restrictions) did not change conclusions. Two RCTs in UK dairy calves compared NSAID monotherapy with antimicrobial monotherapy (RR 1.19, 95% CI 0.72–1.97; very low certainty). Re-treatment is an indirect outcome and may not capture analgesia, fever reduction, or growth effects. Conclusions Across RCTs, NSAID use did not confer a clinically relevant reduction in re-treatment when added to antimicrobials, and evidence is very uncertain for NSAID monotherapy versus antimicrobials. Future trials should include validated pain/welfare measures, clinical and ultrasonographic outcomes, and performance metrics, with pathogen identification to explore effect modification.

Bovine respiratory disease (BRD) is a leading cause of illness and death in cattle and a major driver of antimicrobial use. This systematic review and meta-analysis assessed the clinical effectiveness of five commonly used antimicrobial classes (penicillins, tetracyclines, phenicols, macrolides, and fluoroquinolones) in the treatment of cattle with natural BRD. Cattle from all production systems (feedlot, dairy, slaughter, and stocker) were included, and metaphylaxis trials were excluded. Peer-reviewed trials were searched in several databases, and all reports were screened in duplicate for data extraction and risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was employed to evaluate the certainty of evidence. Twenty-eight randomized controlled trials were included. We did not detect clinically meaningful differences between antimicrobial classes in reducing the need for re-treatment (a surrogate for short-term therapeutic failure). Certainty of evidence ranged from very low to moderate, and results should be interpreted cautiously. Subgroup estimates were broadly consistent for production systems (feedlot and non-feedlot) and for trials with Mycoplasma-positive animals; however, these subgroup analyses were small and imprecise and do not allow firm conclusions. Mortality, relapse, and growth outcomes were measured inconsistently and could not be reliably pooled. Overall, we did not identify any class with a clinically meaningful short-term advantage based on our prespecified thresholds. The results of this systematic review and meta-analysis will inform the BRD Antimicrobial Use Guidelines of the European Network for Optimization of Antimicrobial Therapy (ENOVAT).

Background: Atypical porcine pestivirus (APPV), genus Pestivirus , is the causative agent of congenital tremor type A-II, a neurological disease in newborn piglets that is characterized by tremors. Although the virus can spread horizontally, clinical disease is observed only after in utero infection. While venereal transmission has been proposed as a potential route, the pathogenesis and transmission dynamics of APPV remain incompletely understood. In this study, we aimed to investigate the presence of APPV in semen from Norwegian breeding boars, its temporal shedding patterns, and the potential impact of APPV on semen producing organs. Results: An initial screening of 110 breeding boars revealed that 50.9% (56/110) were APPV-positive in semen, as determined by reverse transcription quantitative PCR (RT-qPCR). The virus load in semen was highly variable, with concentrations up to 4.0 × 10^6 genomic copies (GC)/mL. Extended sampling of a smaller subset of APPV-positive boars ( n = 19) revealed that virus shedding in semen typically persisted for less than 3 months, although intermittent shedding for up to 7 months was observed in one boar. At slaughter, the virus was detected in reproductive organs and accessory glands - even in boars with negative semen and serum samples - but it was not associated with histopathological lesions. Conclusions: As artificial insemination (AI) is widely used in all tiers of pig production, APPV-positive semen from breeding boars may represent an important source of virus transmission. To assess the viability of APPV in AI semen and clarify its potential role in transmission, further research, such as virus isolation for infectivity studies and experimental infections in naïve sows, are required.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as ancillary therapy for bovine respiratory disease (BRD) alongside antimicrobials, and interest in NSAID monotherapy has grown amid antimicrobial stewardship and welfare concerns. We evaluated the clinical effectiveness of NSAIDs for BRD as adjunctive or sole therapy. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in cattle with naturally occurring BRD. Databases searched were MEDLINE (Ovid), Embase (Ovid), CAB Abstracts (Ovid), Biological Abstracts (Ovid), Web of Science Core Collection, and Scopus (search: 22 Apr 2024; update: 12 Sep 2025). Primary outcomes were short-term treatment failure (need for re-treatment); secondary outcomes included relapse, mortality, adverse events, and performance where available. Random-effects pairwise meta-analyses estimated risk ratios (RRs) with 95% CIs. Risk of bias was assessed with a modified RoB 2.0 tool; certainty of evidence was appraised using GRADE. Registration/protocol: this review extends a prior ENOVAT BRD protocol; no separate registration was created. Funding: COST Action CA18217. Results Seventeen RCTs (22 comparisons; 4,909 animals) compared NSAID+antimicrobial versus antimicrobial alone. Adding an NSAID did not reduce re-treatment (RR 0.94, 95% CI 0.84–1.05; I 2 = 0%; moderate certainty). Subgroup (same vs different antimicrobial) and sensitivity analyses (handling of multi-arm trials; follow-up restricted to ≤14 or ≤ 10 days; risk-of-bias restrictions) did not change conclusions. Two RCTs in UK dairy calves compared NSAID monotherapy with antimicrobial monotherapy (RR 1.19, 95% CI 0.72–1.97; very low certainty). Re-treatment is an indirect outcome and may not capture analgesia, fever reduction, or growth effects. Conclusions Across RCTs, NSAID use did not confer a clinically relevant reduction in re-treatment when added to antimicrobials, and evidence is very uncertain for NSAID monotherapy versus antimicrobials. Future trials should include validated pain/welfare measures, clinical and ultrasonographic outcomes, and performance metrics, with pathogen identification to explore effect modification.

Bovine respiratory disease (BRD) is a leading cause of illness and death in cattle and a major driver of antimicrobial use. This systematic review and meta-analysis assessed the clinical effectiveness of five commonly used antimicrobial classes (penicillins, tetracyclines, phenicols, macrolides, and fluoroquinolones) in the treatment of cattle with natural BRD. Cattle from all production systems (feedlot, dairy, slaughter, and stocker) were included, and metaphylaxis trials were excluded. Peer-reviewed trials were searched in several databases, and all reports were screened in duplicate for data extraction and risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was employed to evaluate the certainty of evidence. Twenty-eight randomized controlled trials were included in the final analysis, and no pairwise comparison between antimicrobial classes showed a clinically meaningful effect in reducing the need for re‑treatment. The results were consistent in the subgroup analysis of different production systems (feedlot and non-feedlot) and in trials with Mycoplasma positive animals. Mortality, relapse, and growth outcomes were measured inconsistently and could not be reliably pooled. Overall, certainty ranged from very low to moderate, largely due to indirectness of the outcomes and risk of bias. These findings suggest that commonly used antimicrobial classes have broadly comparable short-term therapeutic performances, without any apparent advantage for those classified as high-priority, critically important antimicrobials in human medicine. The results of this systematic review and meta-analysis will inform the BRD Antimicrobial Use Guidelines of the European Network for Optimization of Antimicrobial Therapy (ENOVAT).

The current pandemic of COVID-19 has highlighted the importance of basic studies on coronaviruses (CoVs) in general, and severe acute respiratory syndrome CoV type 2 (SARS-CoV-2) in particular. CoVs have for long been studied in veterinary medicine, due to their impact on animal health and welfare, production, and economy. Several animal models using coronaviral disease in the natural host have been suggested. In this review, different animal models are discussed, with the main focus on bovine CoV (BCoV). BCoV is endemic in the cattle population worldwide and has been known and studied for several decades. SARS-CoV-2 and BCoV are both betacoronaviruses, where BCoV is highly similar to human coronavirus (HCoV) OC43, encompassing the same virus species (Betacoronavirus 1). BCoV causes respiratory and gastrointestinal disease in young and adult cattle. This review summarizes the current knowledge of the similarities and dissimilarities between BCoV and SARS-CoV-2, as well as discussing the usage of BCoV as a model for human CoVs, including SARS-CoV-2.