Search Results (220)

The yak (Bos grunniens) is a key species in high-altitude rangelands of Asia. Despite their ecological and economic importance, yak production faces persistent challenges, including low milk yields, vulnerability to climate changes, emerging diseases, and a lack of systematic breeding programs. This review presents the genomic, physiological, and environmental dimensions of yak biology and husbandry. Genes such as EPAS1, which encodes hypoxia-inducible transcription factors, underpin physiological adaptations, including enlarged cardiopulmonary structures, elevated erythrocyte concentrations, and specialized thermoregulatory mechanisms that enable their survival at elevations of 3000 m and above. Copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) present promising markers for improving milk and meat production, disease resistance, and metabolic efficiency. F1 and F2 generations of yak–cattle hybrids show superior growth and milk yields, but reproductive barriers, such as natural mating or artificial insemination, and environmental factors limit the success of these hybrids beyond second generation. Infectious diseases, such as bovine viral diarrhea and antimicrobial-resistant and biofilm-forming Enterococcus and E. coli, pose risks to herd health and food safety. Rising ambient temperatures, declining forage biomass, and increased disease prevalence due to climate changes risk yak economic performance and welfare. Addressing these challenges by nutritional, environmental, and genetic interventions will safeguard yak pastoralism. This review describes the genes associated with different yak traits and provides an overview of the genetic adaptations of yaks (Bos grunniens) to environmental stresses at high altitudes and emphasizes the need for conservation and improvement strategies for sustainable husbandry of these yaks. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea in the inpatient and community setting. Real-world data outside the strict environment of randomized controlled trials (RCTs) are needed to improve the quality of evidence. The aim of this study was to compare different clinical outcomes of CDI patients treated with fidaxomicin with those treated with vancomycin using a representative patient population in the United States of America (USA). Methods: Comprehensive real-world data were analyzed for this retrospective observational study, provided by the TriNetX database, an international research network with electronic health records from multiple USA healthcare providers. This includes in- and outpatients treated with fidaxomicin (FDX) or vancomycin (VAN) for CDI between 01/2013 and 12/2023. The following cohorts were compared: (i) patients treated with fidaxomicin within 10 days following CDI diagnosis (FDX group) vs. (ii) patients treated with vancomycin within 10 days following CDI diagnosis (VAN group). Outcomes analysis between the two cohorts was performed after propensity score matching and included event risk and Kaplan–Meier survival analyses for the following concomitant diseases/events occurring during an observational period of 12 months following CDI diagnosis: death, sepsis, candidiasis, infections caused by vancomycin-resistant enterococci, inflammatory bowel disease, cardiovascular disease, psychological disease, central line-associated blood stream infection, surgical site infection, and ventilator-associated pneumonia. Results: Following propensity score matching, 2170 patients were included in the FDX group and VAN groups, respectively. The event risk analysis demonstrated improved outcomes of patients treated with FDX compared to VAN in 6 out of the 10 events that were analyzed. The highest risk ratio (RR) and odds ratio (OR) were found for sepsis (RR: 3.409; OR: 3.635), candidiasis (RR: 2.347; OR: 2.431), and death (RR: 1.710; OR: 1.811). The Kaplan–Meier survival analysis showed an overall survival rate until the end of the 12-month observational period of 87.06% in the FDX group and 78.49% in the VAN group (log-rank p < 0.001). Conclusions: Our comparative event risk analysis demonstrated improved outcomes for patients treated with FDX compared to VAN in most of the observed events and underlines the results of previously conducted RCTs, highlighting the beneficial role of FDX compared to VAN. Further big data analyses from other industrialized countries are needed for comparison with our observations. Full article

Necrotic enteritis, caused by Clostridium perfringens (C. perfringens) is a disease present worldwide and causes major economic losses. The re-emergence of the disease, in recent years, is mainly due to the ban of the usage of antibiotics as growth promoters in the EU. The aim of this study was to establish a reliable, robust challenge model. Ross hybrid broilers were divided into randomized groups: a positive and a negative control group, a group receiving antibiotic treatment and three groups fed with assorted feed supplements, all receiving the same basal diet. The birds in the treatment groups were vaccinated twice using a 10-times dose of an Infectious Bursitis live vaccine and the animals were challenged four times with a NetB toxin producing C. perfringens strain. The presence of clinical signs and body weight gain were monitored. At the end of the study necropsy was performed and the gut lesions were scored. During the experiment, clinical signs were absent in the negative control group and in the antibiotic treated group. The other animals displayed diarrhea and feather loss. These symptoms were the most pronounced in the positive control group. The gut lesion scores showed significant differences between the negative and positive control groups, with the former scoring the lowest. Based on these results, the challenge model establishment was successful and in this setup the assessment of the potency of feed additives is also possible. Full article

Bovine respiratory disease complex (BRDC) is one of the primary causes of morbidity, mortality, and economic loss in cattle worldwide. Accurate and rapid identification of causative pathogenic agents is essential for effective disease management and control. In this study, a novel multiplex fluorescence-based quantitative polymerase chain reaction (qPCR) assay was developed for the simultaneous detection of eight major pathogens associated with BRDC. The targeted pathogens included the following: bovine viral diarrhea virus (BVDV), bovine parainfluenza virus type 3 (BPIV3), bovine respiratory syncytial virus (BRSV), bovine coronavirus (BcoV), Mycoplasma bovis (M.bovis), Pasteurella multocida (PM), Mannheimia haemolytica (MH), and infectious bovine rhinotracheitis virus (IBRV). The assay was rigorously optimized to ensure high specificity with no cross-reactivity among targets. The limit of detection (LOD) was determined to be as low as 5 copies per reaction for all target pathogens. The coefficient of variation (CVs) for both intra-assay and inter-assay measurements were consistently below 2%, demonstrating excellent reproducibility. To validate the clinical utility of the assay, a total of 1012 field samples were tested, including 504 nasal swabs from Farm A and 508 from Farm B in Jiangsu Province. BVDV, BcoV, PM, and MH were detected from Farm A, with a BVDV-positive rate of 21.63% (109/504), BcoV-positive rate of 26.79% (135/504), PM-positive rate of 28.77% (145/504), and MH-positive rate of 15.08% (76/504). Also, BcoV, PM, MH, and IBRV were detected from Farm B, with a BcoV-positive rate of 2.36% (12/508), PM-positive rate of 1.38% (7/508), MH-positive rate of 14.76% (75/508), and IBRV-positive rate of 5.51% (28/508). Notably, a significant proportion of samples showed evidence of mixed infections, underscoring the complexity of BRDC etiology and the importance of a multiplex diagnostic approach. In conclusion, the developed multiplex qPCR assay provides a reliable, rapid, and cost-effective tool for simultaneous detection of multiple BRDC-associated pathogens, which will hold great promise for enhancing disease surveillance, early diagnosis, and targeted intervention strategies, ultimately contributing to improved BRDC management and cattle health outcomes. Full article

Various enteropathies, including immune-mediated (IME) and infection-related conditions, can lead to small intestinal mucosal injury and malabsorption. While immune dysregulation plays a central role in diseases like celiac disease and autoimmune enteropathy, other conditions such as small intestinal bacterial overgrowth (SIBO) and tropical sprue (TS) involve infectious or microbial pathogenesis. Common clinical manifestations include weight loss, chronic diarrhea, and nutritional deficiencies. While celiac disease (CD) remains the most prevalent IME in adults, an expanding spectrum of non-celiac enteropathies has been recognized, including autoimmune enteropathy (AIE), common variable immunodeficiency disease (CVID), olmesartan-induced enteropathy, tropical sprue, and small intestinal bacterial overgrowth. These conditions often present with overlapping clinical, serological, and histological features, complicating their differentiation from CD. Accurate diagnosis is critical for the timely initiation of effective treatment to prevent disease progression and associated complications such as severe malabsorption and enteropathy-associated T-cell lymphoma (EATL). The small intestine plays a dual role in nutrient absorption and immune regulation, making it uniquely vulnerable to immune dysregulation. In IMEs, hyperactive immune responses disrupt intestinal homeostasis, leading to mucosal damage and impaired nutrient absorption. Although CD is the prototypical IME, increasing the recognition of non-celiac IMEs, it highlights the need for a more nuanced approach to small bowel biopsy interpretation. This review explores the histopathological and clinical features of common IMEs, with a focus on distinguishing non-celiac disorders that mimic CD. By enhancing the understanding of these conditions, this review aims to improve diagnostic accuracy, facilitate appropriate therapeutic interventions, and mitigate complications associated with delayed or misdiagnosis. A multidisciplinary approach involving gastroenterologists and pathologists is emphasized to optimize outcomes for patients with IMEs. Immune-mediated enteropathies result from an abnormal immune response of the small intestinal mucosa to non-pathogenic molecules, often leading to malabsorption syndrome. The most common symptoms include weight loss, chronic diarrhea, and nutritional deficiencies. While celiac disease (CD) is the most well-known immune-mediated enteropathy (IME) in adults, other related disorders have been identified in recent years. These conditions share many clinical and histopathological features, therefore making differentiations between them challenging. This study aims to review the most common immune-mediated enteropathies, with a focus on non-celiac disorders that should be considered in the differential diagnosis of celiac disease in small bowel biopsies. Full article

Clostridioides difficile infection (CDI), the most common cause of nosocomial diarrhea, presents with a wide spectrum of clinical manifestations, ranging from mild diarrhea to severe, life-threatening conditions such as pseudomembranous colitis and toxic megacolon. In recent years, both the incidence and severity of CDI have increased, leading to a significant burden in terms of morbidity, mortality, and healthcare costs. We conducted a single-center, retrospective cohort study for 30 months at “Sf. Parascheva” Infectious Diseases Clinical Hospital Iași, in North Eastern Romania, aiming to assess the clinical and laboratory characteristics of CDI, as well as treatment approaches and their association with patient outcomes. A total of 534 patients were included during the study period, of whom 484 had favorable outcomes, while 50 have died of the disease. Fever (p = 0.007) and age over 65 (p = 0.001) were associated with prolonged hospitalization. Patients positive for both A and B toxins and GDH had the highest risk of recurrence (p = 0.020). Among comorbidities, obesity was the only condition significantly linked to recurrence (p = 0.001). In female patients over 65 years old, the probability of survival drops below 60% after 21 days of hospitalization, highlighting a critical risk factor in this population. These results underscore the importance of comprehensive risk assessment in CDI, particularly focusing on advanced age and comorbidities, to guide early therapeutic interventions, optimize patient management, and improve clinical outcomes among high-risk populations. Full article

Infectious bronchitis virus (IBV) and low-pathogenic avian influenza virus (LPAIV) H9N2 are commonly identified in poultry, individually or in association with other pathogens. This study monitored 183 broiler farms affected by respiratory diseases across seven regions of Morocco from January 2021 to December 2023. Among these farms, 87.98% were vaccinated against IBV, while 57.92% were against AI H9N2. Abnormally high mortality rates were observed in 44.26% of the farms, with 24.69% of cases attributed to IBV, 50.62% to LPAI H9N2, and 13.58% due to coinfection with both IBV and H9N2. RT-PCR analysis of tissue samples and cloacal and tracheal swabs collected from 183 broiler farms revealed that 33.33% were positive for IBV and 34.97% for H9N2. Coinfection by IBV and H9N2 was detected in 12.57% of cases, peaking at 17% in 2022. Co-infected flocks exhibited severe clinical signs and lesions, such as reduced food consumption, diarrhea, and renal issues. The predominant lesions were in the respiratory tract, affecting 91.26% of infected broilers. Additionally, among the 183 flocks, 50 farms that tested positive for IBV infection were randomly selected from the seven regions of Morocco for further investigation of other respiratory pathogens, including Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), and infectious laryngotracheitis (ILT), using real-time RT-PCR. Detection rates for these pathogens were 26% for MG, 30% for MS, 4% for ILTv (vaccine strain), and 18% for ILTw (wild strain). Detection rates for single, dual, triple, and quadruple infections were 34%, 42%, 18%, and 4%, respectively. The most common dual and triple coinfections were IBV + H9N2 (14%) and IBV + MG + MS (10%). Phylogenetic analysis of the S gene identified two main IBV genotypes, namely, 793B and D181, with the latter being a strain circulating for the first time in Moroccan poultry. This underscores the urgent need to establish surveillance systems to track pathogen circulation and implement strategies to control virus spread, ensuring the protection of animals and public health. Full article

Background/Objectives: In swine production, the post-weaning period has been identified as one of the most challenging and stressful periods in the life of a piglet due to changes in its environment and feeding regimen. During this period, piglets might undergo infectious challenges with enterotoxigenic Escherichia coli (ETEC) resulting in post-weaning diarrhea (PWD), and meningitis due to Streptococcus suis. Therefore, metaphylactic and curative antimicrobial therapy is frequently applied, which leads to an increased treatment incidence per 100 days at risk (TI₁₀₀). Methods: Here, we report the results of an antimicrobial coaching trajectory in a 1000-sow farm with high antimicrobial use during the post-weaning period. For a period of 21 weeks, we evaluated the effect of an oral live avirulent E. coli F4F18 vaccine (Coliprotec^® F4F18; Elanco AH) for the active immunization of piglets against PWD caused by F4- and F18-ETEC on the reduction in antimicrobial use during the post-weaning period. A 1000-sow farm with PIC sows operating in a 1-week BMS was rated as an ‘attention farm’ at the level of the post-weaning period according to the Antimicrobial Consumption and Resistance in Animals (AMCRA) benchmark reporting tool. To analyze the specific approach towards antimicrobial use and the related post-weaning pathology, a farm visit including a biosecurity check was carried out together with all associated stakeholders. Subsequently, an antimicrobial coaching trajectory was utilized to follow-up on the improvement of the reduction in antimicrobial use after implementation of the various pieces of advice. Results: For analytical purposes, we compared the results obtained in period 1 (P1; vaccination week 1–6) to period 2 (P2; vaccination week 7–21), since practical field experience has demonstrated that a ‘stabilization period’ of about 6 weeks is necessary to obtain the maximal effect of vaccination. There was a significant reduction in mortality (5.7% to 2.0%) and improvement in the average daily weight gain (366 g/d to 392 g/d) following vaccination, with a simultaneous reduction in the number of days in nursery (45 days to 38 days). Meanwhile, the weight at the end of nursery remained at a similar level. There was a clinically relevant though non-significant decrease in the TI₁₀₀ (32.8 days to 20.6 days). Overall, the implementation of all measures resulted in a positive ROI of 2.72 per piglet. Conclusions: The implementation of several biosecurity measures in combination with the use of an oral live avirulent E. coli F4F18 vaccine (Coliprotec F4F18) could improve performance parameters and reduce mortality, while reducing the number of days in nursery and the TI₁₀₀. Overall, a positive return on investment of 2.72 could be obtained per piglet produced under these improved conditions. Full article

Bovine rotavirus (BRV) is one of the main pathogens that cause acute diarrhea in calves under one month of age. Passive immunization has been recognized as an effective way to prevent and treat BRV infection. Recent studies have shown that 10% of bovine antibodies possess an ultra-long CDR H3 domain, which has been shown to be the smallest antigen-binding domain. Due to the extremely small size of ultra-long CDR H3 antibodies, the phage display method was utilized to obtain ultra-long CDR H3 antibodies targeting BRV, providing a new approach for the prevention and/or treatment of BRV. Here, we report the preparation of BRV-specific bovine ultra-long CDR H3 antibodies obtained by constructing and screening a phage display library containing approximately 8.55 × 10⁹ individual clones. Through three rounds of bio-panning, we identified 92 candidate clones, of which 79 exhibited specific binding activity in phage ELISAs. The recombinant bovine ultra-long CDR H3 antibodies could specifically bind to BRV in ELISAs and cell immunofluorescence assays. The neutralizing activity was further confirmed through virus neutralization tests. In the calf model experiment, the recombinant bovine ultra-long CDR H3 antibodies could relieve the symptoms of diarrhea, reduce both the amount and duration of virus release, and increase the survival in calves experimentally infected with BRV. Therefore, BRV-specific bovine ultra-long CDR H3 antibodies could serve as an effective agent for the prevention and treatment of BRV infection. At the same time, the development of ultra-long CDR H3 antibodies using phage display screening technology provides a new approach for developing biological agents for the prevention and control of infectious diseases in bovines. Full article

Infectious bronchitis virus (IBV) of the GI-23 lineage, which first emerged in the Middle East in the late 1990s, has since spread worldwide. The factors driving its expansion, whether human involvement, wild bird migration, or the virus’s biological traits, are still unclear. This study aimed to trace the genome evolution of GI-23 IBV in chickens and its adaptability to quails, which are susceptible to both gamma- and deltacoronaviruses. Thirty specific-pathogen-free (SPF) birds, aged between two and three weeks, were used. Initially, three birds were inoculated with the G052/2016 IBV via the oculo-nasal route. On the third day post-infection (dpi), oropharyngeal swabs were collected from the whole group, pooled, and subsequently used to infect three next birds. This process was repeated nine more times during consecutive IBV passages (P-I–P-X), and eventually, virus sequencing was performed using Next-Generation Sequencing (NGS). The obtained results showed that quails were not susceptible to the IBV GI-23 lineage, as the virus RNA was detected in low amounts only during the first passage (QP-I) with no further detections in later rounds of IBV passaging. In chickens, only mild diarrhea symptoms appeared in a few individuals. The NGS analysis identified sixty-two single nucleotide variants (SNVs), thirty of which caused amino acid changes, twenty-eight were synonymous, and one SNV introduced a stop codon. Three SNVs were found in untranslated regions. However, none of these SNVs lasted beyond seven passages, with forty-four being unique SNVs. The Shannon entropy values measured during passages varied for pol1a, pol1b, S, 5a, 5b, and N genes, with overall genome complexity peaking at CP-VI and CP-X. The highest complexity was observed in the pol1a (CP-X) and S genes (CP-IV, CP-VI, CP-VIII, and CP-X). Along with the S gene that was under positive selection, eight codons in pol1a were also positively selected. These findings suggest that even in an adapted host, IBV variability does not stabilize without immune pressure, indicating continuous molecular changes within its genome. Full article

Porcine epidemic diarrhea virus (PEDV), a highly infectious alphacoronavirus, has resulted in substantial economic losses within the global swine industry. Existing vaccines and therapeutic agents have proven inadequate in effectively preventing and controlling PEDV. Natural compounds offer distinct advantages in antiviral research due to their abundant availability, diverse biological activities, and low toxicity. In this study, the antiviral properties of the naturally occurring alkaloid 1-deoxynojirimycin (DNJ) against PEDV were examined. The CC₅₀ of DNJ was determined to be 912.5 μM through experimental analysis on Vero-E6 cells. DNJ demonstrated an inhibitory effect on PEDV activity, with a 50% inhibitory concentration (IC₅₀) of 57.76 μM. The compound primarily inhibited PEDV proliferation during the viral life cycle stages of attachment and replication. Moreover, DNJ mitigated the production of reactive oxygen species (ROS) and inflammation associated with PEDV infection. Computational docking predictions suggest that the viral non-structural proteins include Nsp12, Nsp14, and Nsp16 may serve as potential targets for DNJ. Consequently, DNJ represents a promising candidate for the development of novel therapeutic agents against PEDV. Full article

Infectious diarrhea caused by Shigella remains a significant global health concern, and several vaccine candidates are approaching phase III clinical studies in the target population of young children in low- and middle-income countries. The World Health Organization (WHO) has published preferred product characteristics (PPCs) for Shigella vaccines to provide strategic guidance that aids in advancing product development and highlights policy considerations for use in LMIC settings where the vaccine is most needed. However, the selection of appropriate clinical endpoints was not clearly defined within the PPCs and remains an important issue for phase III study design. Previously, an expert panel identified areas of alignment and consensus on many clinical study design components while also recognizing that further discussions and data were required to solidify recommendations on key study design aspects. Therefore, WHO convened a diverse range of stakeholders, including manufacturers, regulators, and policymakers across national, regional, and global levels, with the aim of achieving consensus and soliciting inputs from the regulatory community surrounding vaccine phase III study design considerations. The intent of this report is to outline the key points from those discussions to inform the phase III design strategies and investment decisions of product developers and donors and to share recommendations for next steps. Full article

Background/Objectives: Porcine epidemic diarrhea (PED) is a highly contagious enteric infectious disease that causes severe morbidity and mortality in piglets, posing significant economic losses to the swine industry worldwide. Oral vaccines based on Lactococcus lactis offer a promising approach due to their safety and genetic manipulability. This study aims to develop and evaluate an oral L. lactis-based vaccine expressing the full-length PEDV S protein. Methods: A recombinant L. lactis strain expressing the PEDV S protein was constructed and encapsulated in alginate–chitosan microcapsules. Vaccine stability was tested in simulated digestive fluids, and mice were orally immunized. Immune responses were evaluated by measuring specific antibodies, cytokines, and lymphocyte proliferation. Results: The recombinant L. lactis NZ3900/pNZ8149-S strain successfully expressed the full-length PEDV S protein and maintained stable plasmid inheritance. Oral immunization in mice induced detectable PEDV-specific immune responses. Both encapsulated and non-encapsulated vaccines stimulated the production of IgG and sIgA antibodies, as well as cytokines associated with Th1 and Th2 responses. Notably, encapsulation with alginate–chitosan significantly enhanced bacterial survival in digestive conditions and further amplified immune responses, including higher antibody titers, elevated levels of IFN-γ, IL-4, and IL-10, and greater lymphocyte proliferation, indicating improved immune memory. Conclusions: The oral L. lactis NZ3900/pNZ8149-S vaccine expressing the PEDV S protein effectively induced systemic and mucosal immunity in mice. Encapsulation with alginate–chitosan further enhanced its immunogenicity and stability in gastrointestinal conditions. These results suggest that both the engineered L. lactis strain and the encapsulation strategy contribute to the development of a promising oral vaccine platform for controlling PEDV in swine populations. Full article

Objectives: This article presents a study evaluating the antibody levels against infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea (BVD) in Kazakh Whiteheaded calves born to dams immunized with an experimental inactivated combined vaccine against these infections. The vaccine formulation includes the strains “R-93” (IBR) and “Oregon C₂₄V” (BVD), which are preserved in the microorganism collection of the Research Institute for Biological Safety Problems. Methods: To assess the immune response in newborn calves, blood serum samples were collected before the first intake of colostrum, followed by weekly sampling for 28 weeks post-birth. The antibody response was determined using a virus neutralization assay on MDBK cell cultures and lamb testicle cell cultures. Results: The results demonstrated that the protective antibody level against the IBR virus (≥2 log₂) persisted for up to 25 weeks, while the protective level against the BVD virus (≥3 log₂) remained for 23 weeks. Based on these findings, the vaccine was deemed safe, as it did not induce abortions or clinical manifestations of the diseases. The overall duration of the colostral immunity in calves against the IBR and BVD viruses reached 23 weeks. Conclusions: Therefore, it is recommended that Kazakh Whiteheaded calves be vaccinated with the associated inactivated vaccine against infectious bovine rhinotracheitis and bovine viral diarrhea no earlier than 23 weeks of age. Full article

Clostridioides difficile (C. difficile), a gram-positive, spore-forming bacillus, has emerged as a leading cause of healthcare-associated infections, significantly contributing to infectious diarrhea and increasing healthcare costs. This descriptive, cross-sectional study was conducted among Saudi Arabian nursing staff from July to December 2023 to assess their knowledge and practices related to the diagnosis and management of C. difficile infection (CDI). Data were collected using a modified questionnaire. Overall, 358 nurses were surveyed, and 66% reported knowledge of C. difficile procedures. However, only 30.4% of the respondents correctly classified C. difficile as an anaerobic bacillus, while 42.2% were aware of the organism’s common occurrence in healthy adult volunteers. Additionally, 55.6% of respondents were aware of risk factors and 48.9% could name typical medicines that might cause illness. Only 24.0% acknowledged the cytotoxin test as the gold standard for detection, 26.8% identified hand washing with water and soap as an effective method to prevent the transmission of CDI, and 36.3% identified oral metronidazole as the first-line treatment for CDI. In summary, this study revealed a significant lack of awareness among nurses in Saudi Arabia regarding various aspects of CDI, emphasizing the need for improved education and training to address the knowledge gaps and quality of patient care. Full article