Clostridium Botulinum Research Articles

Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. In vivo experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.

That head lag is impressive! Infantile botulism in the NICU: a case report

BackgroundInfantile botulism (IB) is a devastating and potentially life-threatening neuromuscular disorder resulting from intestinal colonization by Clostridium botulinum and the resultant toxin production. It can present with constipation, descending paralysis, and, potentially, respiratory failure. Botulism is a diagnosis that is more commonly seen in the pediatric intensive care unit (PICU) or on the general pediatric wards and would not typically be managed in the neonatal intensive care unit (NICU), and therefore requires high clinical suspicion to ensure prompt diagnosis and treatment.Case presentationWe discuss a case where an infant from central Pennsylvania presented to a Level IV NICU rather than to the PICU for an evaluation for sepsis and was uniquely diagnosed with IB. The infant presented with poor oral feeding and reduced oral intake, hypothermia, and lethargy. His symptoms progressed into hypoxia and acute respiratory failure. Interestingly, this infant had no known exposure to honey or any other identifiable sources of botulism contact. The infant’s twin brother and the other infants who attended the mother’s in-home daycare remained asymptomatic. This infant was initially evaluated and managed for a potential infectious etiology. However, a diagnosis of IB was suspected, and was later confirmed through the detection of botulinum toxin in the infant’s stools. A high level of suspicion allowed for timely treatment with Botulism Immune Globulin neutralizing antibodies (BabyBIG), even prior to confirmatory testing. We describe the process of obtaining BabyBIG, as well as the natural course of illness after treatment in our patient who ultimately made a complete recovery.ConclusionsThis case highlights the importance of considering infantile botulism as a diagnostic possibility even in the absence of risk factors, and the need for vigilance in diagnosing and treating this rare but potentially life-threatening condition. With timely recognition, subsequent treatment with BabyBIG, and supportive care, infants with infantile botulism can be expected to recover completely. This information is particularly important for neonatologists providing care for infants outside the neonatal period, especially during times of high patient census and resulting overflow of pediatric admissions in the NICU.

Dissecting and tracing the gut microbiota of infants with botulism: a cross sectional and longitudinal study.

Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis. We performed 16S rRNA sequencing of 20 infants' stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants' intestinal microbiota as well as function over time series. We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20°C. botulinum isolates from the patients were typed into ST31 and ST32. Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants.

Microbial Spoilage Organisms in Seafood Products: Pathogens and Quality Control

Consuming contaminated seafood can lead to various bacterial illnesses, either from contamination at the source or during processing and distribution. These illnesses can result from bacterial infection or the ingestion of toxins formed in the food before consumption. However, the distinction between the two causes is not always straightforward. For instance, toxins from Clostridium botulinum and Staphylococcus aureus are preformed in food during bacterial growth, while the toxin from Clostridium perfringens is usually formed when the bacteria sporulate in the intestinal tract. Moreover, the toxin from Vibrio cholerae O1 (and O139) is generated as the bacteria multiply in the intestinal tract. Scombrotoxin, a common illness linked to seafood consumption, is caused by the production of histamine and potentially related substances by certain types of Gram-negative bacteria on histidine-rich fish tissue. This topic is examined in greater detail in another chapter of this book, and therefore will not be extensively discussed here. This paper will explore the various types of bacteria that can lead to illness in humans after consuming seafood, the reported incidence of such infections in specific countries with available data. It will also examine both conventional and molecular methods for detecting, identifying, and categorizing these bacteria. There is growing interest in vibrios as the cause of bacterial illnesses linked to the consumption of bivalve molluscan shellfish and other seafood varieties, with a specific focus on this bacterial group.

The analgesic effects of botulinum neurotoxin by modulating pain-related receptors; A literature review.

Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, have been used for the treatment of various central and peripheral neurological conditions. Recent studies have suggested that BoNTs may also have a beneficial effect on pain conditions. It has been hypothesized that one of the mechanisms underlying BoNTs' analgesic effects is the inhibition of pain-related receptors' transmission to the neuronal cell membrane. BoNT application disrupts the integration of synaptic vesicles with the cellular membrane, which is responsible for transporting various receptors, including pain receptors such as TRP channels, calcium channels, sodium channels, purinergic receptors, neurokinin-1 receptors, and glutamate receptors. BoNT also modulates the opioidergic system and the GABAergic system, both of which are involved in the pain process. Understanding the cellular and molecular mechanisms underlying these effects can provide valuable insights for the development of novel therapeutic approaches for pain management. This review aims to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions by inhibiting the transmission of pain-related receptors.

Comparative Phylogenetic Analysis and Protein Prediction Reveal the Taxonomy and Diverse Distribution of Virulence Factors in Foodborne Clostridium Strains.

Clostridium botulinum and Clostridium perfringens, 2 major foodborne pathogenic fusobacteria, have a variety of virulent protein types with nervous and enterotoxic pathogenic potential, respectively. The relationship between the molecular evolution of the 2 Clostridium genomes and virulence proteins was studied via a bioinformatics prediction method. The genetic stability, main features of gene coding and structural characteristics of virulence proteins were compared and analyzed to reveal the phylogenetic characteristics, diversity, and distribution of virulence factors of foodborne Clostridium strains. The phylogenetic analysis was performed via composition vector and average nucleotide identity based methods. Evolutionary distances of virulence genes relative to those of housekeeping genes were calculated via multilocus sequence analysis. Bioinformatics software and tools were used to predict and compare the main functional features of genes encoding virulence proteins, and the structures of virulence proteins were predicted and analyzed through homology modeling and a deep learning algorithm. According to the diversity of toxins, genome evolution tended to cluster based on the protein-coding virulence genes. The evolutionary transfer distances of virulence genes relative to those of housekeeping genes in C. botulinum strains were greater than those in C. perfringens strains, and BoNTs and alpha toxin proteins were located extracellularly. The BoNTs have highly similar structures, but BoNT/A/B and BoNT/E/F have significantly different conformations. The beta2 toxin monomer structure is similar to but simpler than the alpha toxin monomer structure, which has 2 mobile loops in the N-terminal domain. The C-terminal domain of the CPE trimer forms a "claudin-binding pocket" shape, which suggests biological relevance, such as in pore formation. According to the genotype of protein-coding virulence genes, the evolution of Clostridium showed a clustering trend. The genetic stability, functional and structural characteristics of foodborne Clostridium virulence proteins reveal the taxonomy and diverse distribution of virulence factors.

"Cosmetic" iatrogenic botulism : description of 2 cases in Switzerland

Botulism is a neuro-paralytic syndrome caused by the production of a neurotoxic protein by Clostridium botulinum. It is a rare but potentially fatal poisoning. Symptoms are due to blockage of neurotransmitter release at the neuromuscular junction. Botulism usually occurs following ingestion, inhalation or contact of the toxin with a wound. More recently, cases of iatrogenic botulism have been described, notably following the injection of toxin for therapeutic or cosmetic purposes. In spring 2023, an outbreak of iatrogenic botulism following intragastric injections was reported in Europe. Here, we provide an overview of botulism, followed by a presentation of the only two Swiss cases reported during the epidemic.

Repurposing FDA-approved disulfiram for targeted inhibition of diphtheria toxin and the binary protein toxins of Clostridium botulinum and Bacillus anthracis.

Many bacteria act pathogenic by the release of AB-type protein toxins that efficiently enter human or animal cells and act as enzymes in their cytosol. This leads to disturbed cell functions and the clinical symptoms characteristic for the individual toxin. Therefore, molecules that directly target and neutralize these toxins provide promising novel therapeutic options. Here, we found that the FDA-approved drug disulfiram (DSF), used for decades to treat alcohol abuse, protects cells from intoxication with diphtheria toxin (DT) from Corynebacterium diphtheria, the causative agent of diphtheria, lethal toxin (LT) from Bacillus anthracis, which contributes to anthrax, and C2 enterotoxin from Clostridium botulinum when applied in concentrations lower than those found in plasma of patients receiving standard DSF treatment for alcoholism (up to 20µM). Moreover, this inhibitory effect is increased by copper, a known enhancer of DSF activity. LT and C2 are binary toxins, consisting of two non-linked proteins, an enzyme (A) and a separate binding/transport (B) subunit. To act cytotoxic, their proteolytically activated B subunits PA63 and C2IIa, respectively, form barrel-shaped heptamers that bind to their cellular receptors and form complexes with their respective A subunits LF and C2I. The toxin complexes are internalized via receptor-mediated endocytosis and in acidified endosomes, PA63 and C2IIa form pores in endosomal membranes, which facilitate translocation of LF and C2I into the cytosol, where they act cytotoxic. In DT, A and B subunits are located within one protein, but DT also forms pores in endosomes that facilitate translocation of the A subunit. If cell binding, membrane translocation, or substrate modification is inhibited, cells are protected from intoxication. Our results implicate that DSF neither affects cellular binding nor the catalytic activity of the investigated toxins to a relevant extend, but interferes with the toxin pore-mediated translocation of the A subunits of DT, LT and C2 toxin, as demonstrated by membrane-translocation assays and toxin pore conductivity experiments in the presence or absence of DSF. Since toxin translocation across intracellular membranes represents a central step during cellular uptake of many bacterial toxins, DSF might neutralize a broad spectrum of medically relevant toxins.

Botulismo em bovinos no Mato Grosso do Sul: histórico, situação atual e perspectivas

ABSTRACT: Botulism is a neuroparalytic disease caused by ingesting neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum. It is a significant cause of cattle mortality in Brazil. BoNTs block the release of acetylcholine at the neuromuscular synapses and cause muscle flaccidity. The diagnosis of botulism is challenging due to two main factors: the absence of macro and microscopic lesions and the difficulties inherent in laboratory tests considered the gold standard for botulism. Due to these difficulties, reviews of botulism diagnoses in Mato Grosso do Sul and extensively in the Center-West of Brazil became discrepant according to the diagnostic methodology used, making it difficult to correctly assess the disease’s prevalence, epidemiology, and clinical picture. This study aimed to review the diagnoses of botulism in cattle reported in Brazil, comparing the criteria used in each case. We studied the cause, the pathogenesis, clinical signs, and all the diagnosis methods applied to botulism. Based on the subject reviewed, we propose a diagnostic protocol based on standards adequate to the Brazilian circumstances. We also reviewed the critical diseases of cattle diseases to be included in the differential diagnosis of botulism.

The Role Of Bacteria In Microplastic Bioremediation And Implications For Marine Ecosystems

Microplastics are micro particles <5 mm in size that pose a threat to the survival of organisms living on land and in the ocean. Microplastics contain toxic and carcinogenic or persistent chemicals that will directly or indirectly have a negative impact on marine ecosystems. The process of decomposing waste into microplastics takes a very long time that can take hundreds of years. This can be overcome by the use of bacteria using bioremediation techniques to degrade microplastics in the marine ecosystem. With regard to this, this article aims to review the role of bacteria in degrading microplastics and their impact on marine ecosystems. The method used in this article is a literature review by reviewing related and relevant articles as references. The articles obtained will be sorted according to the topic of the role of bacteria in microplastic bioremediation. Furthermore, it will be analyzed and the results used as a reference for the preparation of this article. The results of the review that the author found were that Pseudomonas, Ochrobactrum, Halomonas sp and Clostridium botulinum bacteria were able to become agents of microplastic degradation in the marine ecosystem.

Understanding retort processing: A review.

Retort processing is a food preservation technique to address the challenge posed by Clostridium botulinum for commercial sterility of a food product to get microbiologically safe and stable products by heating. This review aims to explore the journey of retort processing, starting from its early use in single-batch canned foods and progressing to its contemporary applications with different types of containers and heating mediums. Additionally, it will delve into the adaptability of retort equipment, including its ability to operate in stationary and various agitation states, as well as its flexibility in processing speed for both single-batch and continuous operations.

A Novel Prophage-like Insertion Element within yabG Triggers Early Entry into Sporulation in Clostridium botulinum.

Sporulation is a finely regulated morphogenetic program important in the ecology and epidemiology of Clostridium botulinum. Exogenous elements disrupting sporulation-associated genes contribute to sporulation regulation and introduce diversity in the generally conserved sporulation programs of endospore formers. We identified a novel prophage-like DNA segment, termed the yin element, inserted within yabG, encoding a sporulation-specific cysteine protease, in an environmental isolate of C. botulinum. Bioinformatic analysis revealed that the genetic structure of the yin element resembles previously reported mobile intervening elements associated with sporulation genes. Within a pure C. botulinum culture, we observed two subpopulations of cells with the yin element either integrated into the yabG locus or excised as a circular DNA molecule. The dynamics between the two observed conformations of the yin element was growth-phase dependent and likely mediated by recombination events. The yin element was not required for sporulation by C. botulinum but triggered an earlier entry into sporulation than in a related isolate lacking this element. So far, the yin element has not been found in any other C. botulinum strains or other endospore-forming species. It remains to be demonstrated what kind of competitive edge it provides for C. botulinum survival and persistence.

Botulinum neurotoxin type A in the interdisciplinary treatment of sialorrhea in adults and children-update and practice recommendations.

Sialorrhea is defined as a chronic excessive flow of saliva from the mouth, often with adverse consequences for health and quality of life of patients. In addition to currently used non-drug treatment and systemic drugs, intraglandular Botulinum Neurotoxin A (BoNT/A) injections have been examined in case studies, controlled trials and clinical practice. Two pivotal Phase III trials recently led to market approval in the USA and EU for IncobotulinumtoxinA [Xeomin®, IncoBoNT/A, Clostridium botulinum neurotoxin type A (150 kD), free from complexing proteins, Merz Pharmaceuticals GmbH] for treatment of chronic sialorrhea in adults and pediatric patients. This review provides a multidisciplinary approach to discuss the current state of sialorrhea therapy as well as benefits and current limitations of BoNT/A injections. A consensus regarding treatment recommendations made available to physicians in Germany in 2022 has now been updated here for presentation to an international audience. This review provides a framework including a flow chart for patient selection, recommendations for dosing and the injection process, as well as a discussion of therapeutic goals, long-term benefits and safety aspects. This review is aimed at supporting physicians in developing multidisciplinary and individualized treatment approaches to achieve optimal benefits for patients.

Effect of retort processing, containers and motion types on digestibility of black beans (Phaseolus vulgaris L.) starch

SummaryWith the growing demand for convenient and shelf‐stable canned beans, understanding the changes in starch digestibility due to retort processing is crucial for optimising nutritional quality and enhancing consumer health. The present study investigated the impact of retort processing, specifically container type and agitation, on the digestibility of black bean starch. Retort pouches exhibited a more rapid heat transfer rate to the enclosed product than cans, which reduced the overall processing duration. Also, the processing time to achieve a Fo = 6 of Clostridium botulinum was almost 2.5 min (pouches) and 3.2 min (cans) faster for the oscillating than the static mode. The in vitro digestibility data revealed that the retort processing of black beans led to an increase in rapidly digestible starch (RDS) from 10.51% to 32.11%. However, slowly digestible starch (SDS) decreased from 15.67% to 7.89%, and resistant starch (RS) decreased from 47.91% to 11.86%, regardless of the container type and motion involved. Processing enhanced starch digestibility in all the combinations of container and motions; nevertheless, black beans in pouches with oscillatory motion still contain a relatively significant amount of SDS and RS than the other combinations. These findings have important implications for the food industry in optimising processing techniques and packaging strategies to preserve the nutritional value of black beans. The findings of this study can have practical implications for food producers engaged in the retort processing of foods contained in pouches and cans. The investigation will provide insights into how the process of retort sterilisation affects digestibility, including slowly digestible starch and resistant starch of different types of starch.

Botox Treatment: A Comprehensive Review

An exotoxin called botulinum toxin, or Botox, is isolated from Clostridium botulinum. It prevents the cholinergic nerve end plates from releasing acetylcholine, which causes the innervated muscles or glands to become inactive. Botox has proven to be effective for improving facial cosmetics, but new research has shown that it can also be used to treat a variety of surgical and medical disorders that aren't cosmetic. This article examines the available data regarding Botox use for non-cosmetic head and neck problems too. Because of its quick, distinct and long-lasting outcomes for the reduction of facial fine lines and wrinkles and cosmetic rejuvenation, injectable treatments like botulinum toxin are gaining popularity. Excessive sweating or hyperhidrosis can also be treated with Botox. Botox treatment can reduce the frequency of migraines, with chronic migraines requiring treatment in every three months. Additionally, Botox can help in reducing urinary incontinence caused by an overactive bladder. However, the usage of pure botulinum toxin dosages employed by certified healthcare professionals are strictly to be done under the stringent medical guidelines. When handled properly, botulinum toxins utilized in medicine are non- hazardous.

Safety Profile of Botulinum Toxin for Migraine Headache Prophylaxis: A Systematic Review and Meta-analysis

Context: Nowadays, botulinum toxin is used for migraine prophylaxis, and a wide range of adverse effects (AEs) are reported after administration. Objectives: The present study was conducted to evaluate the safety profile of botulinum toxin for migraine headache prophylaxis. Methods: Migraine Disorder, Disorder AND Migraine, Headache AND Sick, Headache AND Migraine, Migraine, Migrainosus, Migraine Headache, Migraines, Sick Headaches, Botulinum, Toxins AND Botulinum, Botulinum AND Neurotoxins, Toxins AND Clostridium Botulinum Neurotoxins, Botulinum Toxin, Botulinum Neurotoxin, Clostridium Botulinum Toxins, and Botulin were searched in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar databases, and gray literature, including references of the studies published before April 2023. Results: We found 3081 articles by literature search; after deleting duplicates, 1711 remained. Thirty-five articles remained for meta-analysis. The pooled prevalence of musculoskeletal weakness in the head and neck regions was 4% (95% CI: 2-5%) (I2 = 92.2%, P < 0.001). The pooled prevalence of neck pain was 6% (95% CI: 4-7%) (I2 = 95.8%, P < 0.001). The pooled prevalence of blepharoptosis was 2% (95% CI: 2-3%) (I2 = 91.1%, P < 0.001). The pooled prevalence of facial paralysis was 2% (95% CI: 1-4%) (I2 = 94.1%, P < 0.001). The pooled prevalence of injection site pain was 4% (95% CI: 2-5%) (I2 = 93.5%, P < 0.001). Conclusions: The results of this systematic review and meta-analysis show that the most common AEs following botulinum toxin injection for migraine headache prophylaxis are neck pain, followed by musculoskeletal weakness and injection site pain.

Efficacy of a New Alcohol-Free Organic Acid-Based Hand Sanitizer against Foodborne Pathogens.

In light of the global health crisis triggered by the COVID-19 pandemic, numerous experts have deemed the utilization of hand sanitizers imperative as a precautionary measure against the virus. Consequently, the demand for hand sanitizers has experienced a substantial surge. Since the beginning of 2020, the utilization of alcohol-free hand sanitizers has been increasingly favored due to the potential risks associated with alcohol poisoning, flammability, as well as the adverse effects on skin lipid dissolution, dehydration, and sebum reduction, which can lead to severe cases of eczema and norovirus infections. In this study, we developed an aqueous hand sanitizer that does not contain alcohol. The sanitizer consists of naturally occurring, food-grade organic acids, including lactic, citric, and azelaic acids. Additionally, food-grade ammonium sulfate and a small amount of povidone-iodine (PVPI) were included in the formulation to create a synergistic and potent antibacterial effect. The effectiveness of the hand sanitizer was evaluated against four common foodborne pathogens, namely Clostridium botulinum, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, via in vitro testing. The organic acids exhibited a synergistic inhibitory function, resulting in a 3-log reduction in CFU/mL. Furthermore, the presence of povidone-iodine and ammonium sulfate enhanced their antibacterial effect, leading to a 4-log reduction in CFU/mL. The hand sanitizer solution remained stable even after 60 days of storage. During this period, the detection of additional triiodide (I3-) ions occurred, which have the ability to release broad-spectrum molecular iodine upon penetrating the cell walls. This alcohol-free hand sanitizer may offer extended protection and is anticipated to be gentle on the skin. This is attributed to the presence of citric and lactic acids, which possess cosmetic properties that soften and smoothen the skin, along with antioxidant properties.

Cellular and population strategies underpinning neurotoxin production and sporulation in Clostridium botulinum type E cultures.

Toxin production and sporulation are key determinants of pathogenesis in Clostridia. Toxins cause the clinical manifestation of clostridial diseases, including diarrhea and colitis, tissue damage, and systemic effects on the nervous system. Spores ensure long-term survival and persistence in the environment, act as infectious agents, and initiate the host tissue colonization leading to infection. Understanding the interplay between toxin production and sporulation and their coordination in bacterial cells and cultures provides novel intervention points for controlling the public health and food safety risks caused by clostridial diseases. We demonstrate environmentally driven cellular heterogeneity in botulinum neurotoxin and spore production in Clostridium botulinum type E populations and discuss the biological rationale of toxin and spore production in the pathogenicity and ecology of C. botulinum. The results invite to reassess the epidemiology of botulism and may have important implications in the risk assessment and risk management strategies in food processing and human and animal health.

Skin Toxicities Associated with Botulin Toxin Injection for Aesthetic Procedures: Data from the European Spontaneous Reporting System.

Botulinum toxin is a protein deriving from the bacteria Clostridium botulinum and it is widely used for the treatment of a variety of muscle hyperactivity syndromes and for cosmetic indications. Having a long-lasting effect, Botulinum toxin type A (BTA) is one of the most botulin toxin products used. Even if BTA has shown benefits in reducing the vertical lines between the eyebrows, Adverse Drug Reactions (ADRs) have been experienced as well, of which the most common ones are headache and drooping eyelids. In addition, since other local and systemic risks have been identified, a non-interventional post-authorization safety study (PASS) has been started. The aim of the present study was to report cases of skin toxicity associated with this drug, considering Individual Case Safety Reports (ICSRs) existing on the Eudravigilance website. Among 1464 ICSRs sent to the EV database, 718 ICSRs, including 5154 PTs, reported BTA as a suspected drug associated with cutaneous toxicity. The majority of patients experiencing BTA-induced skin toxicity were female (92.1%) belonging mostly to the age group of 18-64 years. The most serious criteria, when reported, were "Other Medically Important Condition" and "Caused/prolonged hospitalization", although the outcome was mainly reported as "Unknown". The most reported PTs, related to skin disorders, were: "Erythema", "Rash", "Pruritus", "Urticaria", "Swelling face", "Brow ptosis", "Eyelid ptosis", "Injection site pain", and "Angioedema". Considering that in most ICSRs, ADRs related to skin disorders were symptoms of hypersensitivity reactions which in some conditions could be life-threatening, further studies are required to better define the safety profile of BTA used for aesthetic procedures.

A systematic review to assess the effectiveness of pre-harvest meat safety interventions to control foodborne pathogens in beef

Safe beef is a priority for consumers, policy makers, official veterinarians, and producers. This systematic review aims to update the recent knowledge on pre-harvest interventions to control main foodborne pathogens in beef and to assess their effectiveness. Only controlled trials in beef or dairy cattle were included. A total of 1514 studies were retrieved from PubMed® and Web of ScienceTM for 13 selected pathogens in particular Salmonella and shiga toxin-producing Escherichia coli (STEC). After the screening, 28 papers remained for Campylobacter (n = 1), Clostridium botulinum (n = 1), Clostridium perfringens (n = 1), Extended spectrum-lactamase AmpC gene-carrying bacteria (ESBL/AmpC) (n = 1), Salmonella (n = 11), and STEC (n = 13). Results were synthesised narratively using tables as support. Research on pre-harvest interventions to control foodborne zoonoses in bovines was mostly focused on Salmonella spp. and STEC. The studies retained on Salmonella and STEC showed that vaccination, and cleaning, disinfection, management, and biosecurity were the most tested and effective interventions, denoting their potential to control or reduce detection and shedding of these pathogens. The correct implementation of such measures is crucial for their efficacy. While vaccination can be implemented to prevent severe outcomes of disease and reduce shedding; cleaning, disinfecting and biosecurity can prevent the introduction and/or the spread of pathogens to/within farms. The use of feed additives and treatments had mixed results but seemed to be effective for Salmonella. The criteria for paper selection excluded observational studies which document effective practices like depopulation and repopulation with healthy animals. Overall, high herd health status coupled with good management and biosecurity were effective to control or prevent the important foodborne pathogens in cattle at pre-harvest level.