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Rapidly waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires continued global access to affordable vaccines. Globally, inactivated SARS-CoV-2 vaccines have been widely used during the SARS-CoV-2 pandemic. In this proof-of-concept study we adapted an original-D614G SARS-CoV-2 virus to Vero cell culture as a strategy to enhance inactivated vaccine manufacturing productivity. A passage 60 (P60) virus showed enhanced fitness and 50-fold increased virus yield in a bioreactor compared to the original-D614G virus. It further remained susceptible to neutralization by plasma from SARS-CoV-2 vaccinated and convalescent individuals, suggesting exposure of relevant epitopes. Monovalent inactivated P60 and bivalent inactivated P60/omicron BA.1 vaccines induced neutralizing responses against original-D614G and BA.1 viruses in mice and hamsters, demonstrating that the P60 virus is a suitable vaccine antigen. Antibodies further cross-neutralized delta and BA.5 viruses. Importantly, the inactivated P60 vaccine protected hamsters against disease upon challenge with original-D614G or BA.1 virus, with minimal lung pathology and lower virus loads in the upper and lower airways. Antigenicity of the P60 virus was thus retained compared to the original virus despite the acquisition of cell culture adaptive mutations. Consequently, cell culture adaptation may be a useful approach to increase yields in inactivated vaccine antigen production.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinas de Produtos Inativados , Animais , Células Vero , Chlorocebus aethiops , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Humanos , Proteção Cruzada/imunologia , Cricetinae , FemininoRESUMO
BACKGROUND: Umbilical outpouchings (UOs) in pigs are of welfare and production concern in Danish pig herds. One of the challenges is the transportation of these animals due to the size of the UOs and ulcerations on them. With certain precautions and an approval from a veterinarian, pigs with UOs may be transported, however, UOs are associated with several intra-abdominal lesions, e.g. peritonitis and incarceration, which may worsen during the process of transportation. The prevalence and characterization of intra-abdominal lesions associated with UOs following transportation has not been investigated. Therefore, the objective of the present study was to evaluate lesions associated with the intestines and peritoneum in slaughter pigs with wounded UOs following transportation to an abattoir. RESULTS: A cross-sectional study involving three conventional Danish pig herds was conducted comprising 96 slaughter pigs with wounded UOs transported to an abattoir. Following slaughter the UOs with accompanying intestines were examined pathologically. Three distinct morphological categories were present: hernia, enterocystoma and herniating enterocystoma. Intra-abdominal lesions were present in 72% of the animals, representing 65% (44/68) of the hernias, 77% (10/13) of the enterocystomas, and 100% (15/15) of the herniating enterocystomas. Several different lesions were found like bleedings, acute/chronic peritonitis and hypertrophy of the intestinal muscular layers. CONCLUSIONS: The prevalence of intra-abdominal lesions in pigs transported with a wounded UO was found to be high independent of the underlying condition, and it is clear that these pigs possess a vulnerable group of animals, especially during physical stressful situations like transportation. More information is needed regarding the prevalence of intra-abdominal lesions in UO pigs without wounds on the UO. The results provide valuable knowledge, that can be used when examining and evaluating UO pigs before transportation.
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The aim of the study was to characterise and determine the prevalence of band-shaped tail lesions in Holstein cows. Lesions were present either as wounds or by epithelised granulation/connective tissue formations. Both types were characterised by a median localisation 7 cm from the tip of the tail, and they occurred on the dorsal aspect of the tail. From here they encircled the tail either completely or in varying degrees, and they were often present as isolated lesions (93%). The prevalence of band-shaped tail lesions was found to be 25% among 2099 cows examined in 16 Danish Holstein herds with a variation from 18 to 40% between herds. In the herds, the wound lesions and the connective tissue formations accounted for 22% and 78% of all band-shaped tail lesions, respectively. Among 458 Holstein cows examined at an abattoir the prevalence of band-shaped tail lesions was 23%, i.e. similar to the prevalence within the herds. At the abattoir the share of band-shaped wound lesions was 67% and the band-shaped connective tissue formation 33%. Associations between the occurrence of band-shaped tail lesions and parity and lack of the tail tip were observed.
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Doenças dos Bovinos , Cauda , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/patologia , Prevalência , Feminino , Dinamarca/epidemiologiaRESUMO
INTRODUCTION: Histology of debrided bone tissue is a confirmatory diagnostic criterion for fracture related infection (FRI) and prosthetic joint infection (PJI). The aim of the present study was to describe the histopathology of the first and last debrided bone tissue in chronic osteomyelitis (CO) according to the international diagnostic guidelines for FRI and PJI. METHODS: 15 patients with CO were allocated to surgical treatment using a one-stage protocol including extensive debridement. Suspected infected bone tissue eradicated early in the debridement procedure was collected as a clearly infected sample (S1). Likewise, the last eradicated bone tissue was collected as a suspected non-infected sample (S2). The samples were processed for histology. HE-stained sections were patho-morphologically examinated. Immunohistochemistry with MAC-387 antibodies towards calprotectin was used for estimation of neutrophil granulocyte (NP) score (0, 1, 2 or 3). RESULTS: S1 samples showed a mean NP score of 2.6 (3 is confirmatory for infection). Following debridement, the NP score was significantly (p = 0.005) reduced to a mean NP score of 1.6. The S1 samples showed a mix of fibrovascular tissue, dense fibrosis, viable bone, bone necrosis and bone debris. S2 samples contained mostly viable bone tissue, however, often small fragments of necrotic bone or bone debris were present. CONCLUSION: The inflammatory response of CO still exists after debridement, although the response fades from the center. Therefore, sampling of debrided bone tissue for histology must be performed initially during surgery, otherwise there is a risk for underestimation of NP infiltration. The present results might also be highly relevant for FRI and PJI.
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Fraturas Ósseas , Osteomielite , Humanos , Infiltração de Neutrófilos , Fraturas Ósseas/cirurgia , Osteomielite/cirurgia , Osteomielite/tratamento farmacológico , Osso e Ossos , Desbridamento/métodos , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Post-weaning diarrhoea (PWD) is a multifactorial condition and the most well documented infectious cause is enterotoxigenic Escherichia coli. The objective of the study was to investigate possible associations between pathological manifestations and pathogens in pigs with and without PWD. The study was conducted as a case-control study and included a total of 173 pigs from 9 different commercial intensive indoor production herds in eastern Denmark. RESULTS: Based on clinical examination, a total of 89 piglets with PWD (cases) and 84 piglets without PWD (controls) were included. Most of the pigs (n = 105/173) presented gastric lesions, which were more frequently observed in the control group. The odds of gastric ulcers were lower among pigs with PWD compared to pigs without PWD with an odds ratio (OR) of 0.2 (0.0; 0.7). Abnormal content in the colon was associated with PWD, with an OR of 6.5 (3.2; 14.3). No apparent association was found between lesions and the various pathogens or a combination of these. The odds of neutrophilic granulocyte infiltration were lower in the jejunum among pigs with PWD (OR 0.3 [0.1; 0.6]) compared to pigs without PWD. The association between neutrophilic granulocyte infiltration in jejunum and PWD differed between the herds (P = 0.03). Furthermore, the associations between PWD and hyperleukocytosis (P = 0.04) or infiltration of eosinophilic granulocytes (P = 0.04) in ileum were also herd dependent. Histopathology revealed several lesions not relatable to PWD. CONCLUSION: The association between lesions and specific pathogens or PWD is more complex than anticipated.
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Infecções por Escherichia coli , Doenças dos Suínos , Animais , Suínos , Infecções por Escherichia coli/veterinária , Estudos de Casos e Controles , Diarreia/veterinária , Diarreia/patologia , Trato Gastrointestinal , Jejuno , Doenças dos Suínos/patologiaRESUMO
BACKGROUND: Recently, in-feed medicinal zinc has been phased out in pig production in the European Union. This makes updated knowledge about porcine post-weaning diarrhea (PWD) crucial. The objectives of the present study were to investigate (i) the clinical presentation of PWD in pigs housed in Danish herds that did not use medicinal zinc, specifically the prevalence of diarrhea and whether PWD was associated to clinical signs of dehydration or altered body temperature; (ii) which microorganism are associated to PWD; and iii) whether measurements of the fecal pH have a potential to be used diagnostically to differentiate between infectious etiologies in cases of PWD. RESULTS: The prevalence of diarrhea varied considerably between the outbreaks in the nine studied herds (median = 0.58, range = 0.10; 0.94). In a cross-sectional design (n = 923), diarrhea was associated with reduced rectal temperature and alkaline feces. Diarrhea was also associated with observably reduced skin elasticity, possibly indicating dehydration. In both diarrheic case pigs (n = 87) and control pigs (n = 86), the presence of Brachyspira pilosicoli, Clostridium perfringens, Cryptosporidium spp., Cystoisopora suis, enterotoxigenic Escherichia coli, Lawsonia intracellularis, porcine circovirus types 2 and 3, rotavirus A, B, C, and H, Samonella enterica spp. enterica, and Trichuris suis was described. PWD was associated with high levels of enterotoxigenic E. coli shedding (odds ratio versus no E. coli detection = 4.79 [CI 1.14; 12.62]). Diarrhea was associated with high levels of rotavirus A shedding (odds ratio versus no/low rotavirus A = 3.80 [CI 1.33; 7.97]). The association between microbiological findings in diarrheic pigs and fecal pH was negligible. CONCLUSIONS: Enterotoxigenic E. coli was confirmed to be a cause of PWD; however, cases of PWD where enterotoxigenic E. coli was not detected in high levels occurred commonly, and this adds to the increasing evidence suggesting that PWD is not necessarily a result of enteric colibacillosis. Rotaviral enteritis might be a differential diagnosis of PWD. pH-measurements cannot be used to differentiate between differential diagnoses for PWD.
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BACKGROUND: Diagnosing and treatment of diseases in pigs are important to maintain animal welfare, food safety and productivity. At the same time antimicrobial resistance is increasing, and therefore, antibiotic treatment should be reserved for individuals with a bacterial infection. The aim of the study was to investigate gross and histological lesions and related pathogens in pigs that died during the nursery period in five Danish farms. In addition, high throughput, real-time qPCR monitoring of specific porcine pathogens in fecal sock and oral fluid samples were carried out to investigate the between-farm and between-batch variation in the occurrence of pathogens. RESULTS: Twenty-five batches of nursery pigs from five intensive, indoor herds were followed from weaning (approximately four weeks) to the end of nursery (seven to eight weeks post weaning). Gross and histological evaluation of 238 dead and 30 euthanized pigs showed the highest prevalence of lesions in the skin, respiratory system, gastrointestinal tract, and joints. Gross and histological diagnoses of lung and joint lesions agreed in 46.5% and 62.2% of selected pigs, respectively. Bacteriological detection of Escherichia coli, Streptococcus suis or Staphylococcus aureus infections in joints, lungs and livers was confirmed as genuine infection on immunohistochemical staining in 11 out of 70 tissue sections. The real-time qPCR analysis of pooled samples showed that most pathogens detected in feces and in oral fluid in general followed the same shedding patterns in consecutive batches within herds. CONCLUSIONS: Gross assessment should be supplemented with a histopathological assessment especially when diagnosing lesions in the lungs and joints. Moreover, microbiological detection of pathogens should optimally be followed up by in situ identification to confirm causality. Furthermore, routine necropsies can reveal gastric lesions that may warrant a change in management. Real-time qPCR testing of fecal sock samples and oral fluid samples may be used to monitor the infections in the individual herd and testing one batch seems to have a good predictive value for subsequent batches within a herd. Overall, optimal diagnostic protocols will provide a more substantiated prescription of antibiotics.
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BACKGROUND: In the pig production, diarrhea can occur during different growth stages including the period 4-16 weeks post weaning, during which a diarrheal outbreak also termed as colitis-complex diarrhea (CCD) can occur and it is distinct from post-weaning diarrhea (1-2 weeks post weaning). We hypothesized that CCD in growing pigs is associated with changes in colonic microbiota composition and fermentation patterns, and the aim of the present observational study was to identify changes in digesta-associated bacteria (DAB) and mucus-associated bacteria (MAB) in the colon of growing pigs with and without diarrhea. A total number of 30 pigs (8, 11, and 12 weeks of age) were selected; 20 showed clinical signs of diarrhea and 10 appeared healthy. Based on histopathological examination of colonic tissues, 21 pigs were selected for further studies and classified as follows: without diarrhea, no colon inflammation (NoDiar; n = 5), with diarrhea, without colonic inflammation (DiarNoInfl; n = 4), and with diarrhea, with colonic inflammation (DiarInfl; n = 12). Composition (based on 16S rRNA gene amplicon sequencing) and fermentation pattern (short-chain fatty acids; SCFA profile) of the DAB and MAB communities were characterized. RESULTS: The DAB showed higher alpha diversity compared to MAB in all pigs, and both DAB and MAB showed lowest alpha diversity in the DiarNoInfl group. Beta diversity was significantly different between DAB and MAB as well as between diarrheal groups in both DAB and MAB. Compared to NoDiar, DiarInfl showed increased abundance of various taxa, incl. certain pathogens, in both digesta and mucus, as well as decreased digesta butyrate concentration. However, DiarNoInfl showed reduced abundance of different genera (mainly Firmicutes) compared to NoDiar, but still lower butyrate concentration. CONCLUSION: Diversity and composition of MAB and DAB changed in diarrheal groups depending on presence/absence of colonic inflammation. We also suggest that DiarNoInfl group was at the earlier stage of diarrhea compared with DiarInfl, with a link to dysbiosis of colonic bacterial composition as well as reduced butyrate concentration, which plays a pivotal role in gut health. This could have led to diarrhea with inflammation due to a dysbiosis, associated with an increase in e.g., Escherichia-Shigella (Proteobacteria), Helicobacter (Campylobacterota), and Bifidobacterium (Actinobacteriota), which may tolerate or utilize oxygen and cause epithelial hypoxia and inflammation. The increased consumption of oxygen in epithelial mucosal layer by infiltrated neutrophils may also have added up to this hypoxia. Overall, the results confirmed that changes in DAB and MAB were associated with CCD and reduced butyrate concentration in digesta. Moreover, DAB might suffice for future community-based studies of CCD.
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Disbiose , Microbioma Gastrointestinal , Suínos , Animais , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Bactérias/genética , Diarreia/veterinária , Inflamação , ButiratosRESUMO
Escherichia coli constitutes a major challenge to poultry even when the prevalence of colibacillosis is low. Additionally, specific E. coli strains can severely enhance the detrimental effects on productivity, animal welfare and antimicrobial use. In 2019-2020, a dramatic increase in colibacillosis occurred among Danish broilers causing late-onset mortality and high slaughter condemnations. In the present study, the pathology and causative E. coli-types were characterised. Furthermore, the outbreak-related strains were compared to isolates from concurrent "background" colibacillosis. During the study, 1039 birds were subjected to a comprehensive post-mortem examination, and a total of 349 E. coli isolates were sequenced and characterised by multi-locus sequence typing, virulence and resistance gene presence, plasmid replicon content and phylogenetic analysis. Productivity data from outbreak flocks revealed a mortality of 6.34% ± 3.74 and a condemnation of 5.04% ± 3.67. Contrary, the numbers were 3.18% ± 1.57% and 1.02% ± 0.4 among non-outbreak flocks, respectively. Major lesions were cellulitis (46.82%), airsacculitis (67.63%), pericarditis (55.49%), perihepatitis (41.04%) and femoral head necrosis with physeal/metaphyseal involvement (44.51%). Among non-outbreak broilers, the prevalence was 4.46%, 7.64%, 7.01%, 3.82% and 8.28%, respectively. ST23 and ST101 dominated heavily in outbreak flocks, whereas non-outbreak related isolates consisted of various other STs. A low level of resistance markers was evident, except in few multidrug-resistant isolates. Within ST23 and ST101, 13 and 12 virulence genes were significantly over-represented compared to non-outbreak isolates. In conclusion, clonal lineages were documented as the cause of a devastating outbreak of colibacillosis with great prospects for future interventions.
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Infecções por Escherichia coli , Doenças das Aves Domésticas , Animais , Escherichia coli , Galinhas/genética , Tipagem de Sequências Multilocus/veterinária , Filogenia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/veterinária , Dinamarca/epidemiologia , Doenças das Aves Domésticas/epidemiologiaRESUMO
Two chronic osteomyelitis patients, a diabetic foot osteomyelitis patient and a fracture-related infection patient, all with staphylococci-positive microbiology, were examined to confirm the clinical relevance of bacterial invasion of the submicron osteocyte lacuna-canaliculi network (OLCN) in bone tissue. Based on immunohistochemistry and light microscopy both Staphylococcus aureus and Staphylococcus epidermidis were identified within the OLCN of all four patients. The findings consolidate that bacterial OLCN invasion is a clinically relevant part of osteomyelitis disease biology, which from experimental porcine infections, seems to be time depending. The microscopy pictures of the four patients significantly add to visualize the phenomenon of bacterial OLCN invasion.
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Osteomielite , Infecções Estafilocócicas , Animais , Suínos , Osteócitos/microbiologia , Osteomielite/microbiologia , Staphylococcus aureus , Staphylococcus , Infecções Estafilocócicas/microbiologia , BiologiaRESUMO
SARS-CoV-2 continues to pose a threat to human health as new variants emerge and thus a diverse vaccine pipeline is needed. We evaluated SARS-CoV-2 HexaPro spike protein formulated in Alhydrogel® (aluminium oxyhydroxide) in Syrian hamsters, using an accelerated two dose regimen (given 10 days apart) and a standard regimen (two doses given 21 days apart). Both regimens elicited spike- and RBD-specific IgG antibody responses of similar magnitude, but in vitro virus neutralization was low or undetectable. Despite this, the accelerated two dose regimen offered reduction in viral load and protected against lung pathology upon challenge with homologous SARS-CoV-2 virus (Wuhan-Hu-1). This highlights that vaccine-induced protection against SARS-CoV-2 disease can be obtained despite low neutralizing antibody levels and suggests that accelerated vaccine schedules may be used to confer rapid protection against SARS-CoV-2 disease.
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COVID-19 , SARS-CoV-2 , Animais , Cricetinae , Humanos , Hidróxido de Alumínio , Mesocricetus , COVID-19/prevenção & controle , Vacinação , Anticorpos NeutralizantesRESUMO
Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used. However, poor vaccination accessibility and waning immunity maintain the pandemic, driving emergence of variants. We developed an inactivated SARS-CoV-2 (I-SARS-CoV-2) vaccine based on a viral isolate with the Spike mutation D614G, produced in Vero cells in a scalable bioreactor, inactivated with ß-propiolactone, purified by membrane-based steric exclusion chromatography, and adjuvanted with MF59-like adjuvant AddaVax. I-SARS-CoV-2 and a derived split vaccine induced persisting neutralizing antibodies in mice; moreover, lyophilized antigen was immunogenic. Following homologous challenge, I-SARS-CoV-2 immunized hamsters were protected against disease and lung pathology. In contrast with reports for widely used vaccines, hamster plasma similarly neutralized the homologous and the Delta (B.1.617.2) variant viruses, whereas the Omicron (B.1.1.529) variant was neutralized less efficiently. Applied bioprocessing approaches offer advantages regarding scalability and production, potentially benefitting worldwide vaccine coverage.
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Escherichia coli represents a significant challenge to the poultry industry due to compromised animal welfare, vast productivity losses, elevated mortality, and increased use of antimicrobial compounds. Therefore, effective preventive strategies and insight into the pathogenesis and disease mechanisms of colibacillosis are essential to secure a healthy poultry production. Consequently, discriminative in vivo models of colibacillosis are prerequisite tools for evaluating e.g., preventive measures, exploring novel treatments and understanding disease development. Numerous models of colibacillosis are applied for experimental studies in poultry. Yet, few studies provide a proper characterisation of the model enabling other authors to reproduce experiments or use the model in general. The present paper provides a literature review on avian in vivo models of primary colibacillosis.
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Infecções por Escherichia coli , Aves Domésticas , Animais , Infecções por Escherichia coli/veterinária , Escherichia coli , Antibacterianos , Bem-Estar do AnimalRESUMO
Vitamin C (vitC) deficiency has been associated with an increased risk of cardiovascular disease; while several putative mechanistic links have been proposed, functional evidence supporting a causal relationship is scarce. In this study, we investigated how vitC deficiency affects coronary artery vasomotor function and the development of coronary atherosclerotic plaques in guinea pigs subjected to chronic dyslipidemia by a high-fat diet regime. Female Hartley guinea pigs were fed either a control (low-fat diet and sufficient vitC) (N = 8) or a high-fat diet with either sufficient (N = 8) or deficient (N = 10) vitC for 32 weeks. Guinea pigs subjected to the high-fat diet developed significant atherosclerotic plaques in their coronary arteries, with no quantitative effect of vitC deficiency. In isolated coronary arteries, vasomotor responses to potassium, carbachol, nitric oxide, or bradykinin were studied in a wire myograph. Carbachol, bradykinin, and nitric oxide mediated relaxation in the coronary arteries of the control group. While vasorelaxation to carbachol and nitric oxide was preserved in the two high-fat diet groups, bradykinin-induced vasorelaxation was abolished. Interestingly, bradykinin induced a significant contraction in coronary arteries from vitC-deficient guinea pigs (p < 0.05). The bradykinin-induced contraction was unaffected by L-NAME but significantly inhibited by both indomethacin and vitC, suggesting that, during vitC deficiency, increased release of arachidonic acid metabolites and vascular oxidative stress are involved in the constrictor effects mediated by bradykinin. In conclusion, the present study shows supporting evidence that poor vitC status negatively affects coronary artery function.
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Chlorosphaerolactylate B, a newly discovered antimicrobial halometabolite from the cyanobacterium Sphaerospermopsis sp. LEGE 00249 has been synthesized in three steps by using 12-bromododecanoic acid as starting material. A total of 0.5 g was produced for in vitro and in vivo antimicrobial efficacy testing. In vitro, the minimal inhibitory concentration (MIC) was estimated to be 256 mg/L for Staphylococcus aureus, while the minimal biofilm inhibitory concentration (MBIC) was estimated to be 74 mg/L. The in vivo study utilized a porcine model of implant-associated osteomyelitis. In total, 12 female pigs were allocated into 3 groups based on inoculum (n = 4 in each group). An implant cavity (IC) was drilled in the right tibia and followed by inoculation and insertion of a steel implant. All pigs were inoculated with 10 µL containing either: 11.79 mg synthetic Chlorosphaerolactylate B + 104 CFU of S. aureus (Group A), 104 CFU of S. aureus (Group B), or pure saline (Group C), respectively. Pigs were euthanized five days after inoculation. All Group B animals showed macroscopic and microscopic signs of bone infection and both tissue and implant harbored S. aureus bacteria (mean CFU on implants = 1.9 × 105). In contrast, S. aureus could not be isolated from animals inoculated with saline. In Group A, two animals had a low number of S. aureus (CFU = 6.7 × 101 and 3.8 × 101, respectively) on the implants, otherwise all Group A animals were similar to Group C animals. In conclusion, synthetic Chlorosphaerolactylate B holds potential to be a novel antimicrobial and antibiofilm compound.
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BACKGROUND: Licensed vaccines against SARS-CoV-2 effectively protect against severe disease, but display incomplete protection against virus transmission. Mucosal vaccines providing immune responses in the upper airways are one strategy to protect against transmission. METHODS: We administered Spike HexaPro trimer formulated in a cationic liposomal adjuvant as a parenteral (subcutaneous - s.c.) prime - intranasal boost regimen to elicit airway mucosal immune responses and evaluated this in a Syrian hamster model of virus transmission. FINDINGS: Parenteral prime - intranasal boost elicited high-magnitude serum neutralizing antibody responses and IgA responses in the upper respiratory tract. The vaccine strategy protected against virus in the lower airways and lung pathology, but virus could still be detected in the upper airways. Despite this, the parenteral prime - intranasal booster vaccine effectively protected against onward SARS-CoV-2 transmission. INTERPRETATION: This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies. FUNDING: This work was primarily supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.
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COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunoglobulina ARESUMO
In broiler breeders, background mortality is rarely addressed, however, it represents the death of a vast number of birds, a constant productivity loss, welfare concerns and it might affect chick quality. The study aimed to unveil lesions leading to mortality in a study population perceived as healthy, combined with whole-genome sequencing (WGS) of Escherichia coli, a well-known contributor to disease problems in poultry. Broiler breeders (n = 340) originating from three distinct, putative healthy flocks and their progeny (n = 154) were subjected to a comprehensive post-mortem examination, bacteriological sampling, and sequencing of 77 E. coli isolates. Productivity data confirmed an exemplary health status of the enrolled flocks, and post-mortem examination further verified the absence of general disease problems. Among the submitted broiler breeders, exudative peritonitis (31.2%) was the most frequent lesion linked to infectious disease, whereas airsacculitis, pericarditis, perihepatitis, and salpingitis occurred in 18.5%, 3.5%, 3.8% and 17%, respectively. Yolksacculitis occurred in 15.6% of the broilers, whilst pericarditis, perihepatitis and peritonitis were diagnosed in 9.7%, 7.1% and 9.1%, respectively. WGS revealed a diverse population where ST95 dominated the population retrieved from broiler breeders, whereas ST10 was highly prevalent among broilers. Both lineages could be isolated from extraintestinal sites of birds without lesions indicative of infection. In general, the genetic diversity within flocks was comparable to the diversity between farms, and the overall occurrence of resistance markers was low. In conclusion, a comprehensive insight into lesions associated with background mortality is presented, together with a vast diversity of E. coli isolated from extraintestinal sites during a non-outbreak situation.
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Infecções por Escherichia coli , Pericardite , Peritonite , Doenças das Aves Domésticas , Animais , Galinhas , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/veterinária , Feminino , Genômica , Estudos Longitudinais , Pericardite/veterinária , Peritonite/veterinária , Doenças das Aves Domésticas/epidemiologiaRESUMO
Major geographical transmission of porcine reproductive and respiratory syndrome virus (PRRSV) occurs via semen when a boar stud is infected. This happened in Denmark in 2019, providing an opportunity to compare previous experimental PRRSV boar studies with natural PRRSV-1 infection in boars. The aim of this study was to investigate the association between the presence of PRRSV RNA in serum, semen, testicles, and epididymis of boars naturally infected with PRRSV and to describe the histological lesions in the testes and epididymis combined with direct visualisation of PRRSV-infected cells by immunohistochemical staining (IHC). The exact timing of infection of each boar was not determined, but based on serology the boars were divided into two groups: acute and late infections. All boars included were sampled the same day. In this study, 35 boars and 10 healthy boars from another PRRSV-negative boar stud were included as histological controls. PRRSV RNA was found most often in serum (51%) and least frequently in semen (22%) and was more often detected in the reproductive tract in the acute phase of infection (p < 0.0001; RR: 2.58). Mononuclear cells and multinuclear giant cells were present in the adluminal compartment of the testis and epididymis in PRRSV-infected boars, but not in control boars (p < 0.05), which supports the hypothesis that macrophages are involved in the venereal spread of the virus.
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Biomarkers of inflammation are valuable tools for health status evaluation in numerous species. However, in poultry, methods for measuring acute phase proteins (APP) are sparse and rely on manual laboratory labour reserving these parameters mainly for research studies with APP as a focus point. To extend the use of APP beyond tightly focused research studies, blood from experimentally infected and control hens was analysed using equipment available in many veterinary clinics in order to identify easily accessible biomarkers of infection. Blood samples from broiler breeders (n = 30) inoculated intratracheally with either Escherichia coli or sterile vehicle were randomly selected at 2, 4 and 7 days post-infection (dpi) and subjected to biochemical analysis. Samples for bacteriological testing were collected, and all animals were subjected to a full necropsy for disease confirmation. Significantly higher levels of serum amyloid A were evident in the infected birds at 2 and 4 dpi (p < 0.01) compared to the controls. Likewise, haptoglobin (PIT54) levels were significantly elevated at 4 dpi (p < 0.01) in the infected animal, whilst at 2 dpi magnesium and calcium were significantly lower in the infected group (p < 0.05). Gross pathology and bacteriology confirmed the presence of infection in the E. coli inoculated birds. In conclusion, equipment routinely used in other species for rapid analysis of blood samples, successfully differentiated between sick and healthy birds, hereby, showing great potential as an easily added parameter of evaluation in research studies, and as a valuable decision-making tool for poultry veterinarians.
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Infecções por Escherichia coli , Proteína Amiloide A Sérica , Animais , Galinhas/microbiologia , Escherichia coli , Infecções por Escherichia coli/veterinária , Feminino , HaptoglobinasRESUMO
Animal models of invasive fungal infections have been developed and are applied in a huge number of different animal species for a number of research purposes, for example, the study of pathogenesis, defense mechanisms, and therapeutic strategies. From the different models, which in most cases are based on the same fungal species and often the same strain, as in spontaneous human infections, fundamental results and knowledge of the diagnosis, progression, prophylaxis, and therapy have been achieved. However, in all models, one should be critical with respect to mimicking the disease entity of humans, which is often the focus of the research. In many of the models for instance, the time course is different to the one of humans, and in others, the propensity for localization and containment in specific organs does not parallel the situation in humans. Nevertheless, many animal models of invasive mycoses have proven valuable in a number of research areas. With regard to new generations of anti-mycotic drugs, the models play an essential role in demonstrating antifungal activity, as well as in demonstrating the absence of toxic side effects, a critical step which cannot be accomplished by in vitro studies.