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1.
Res Sq ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38659948

RESUMEN

The use of antimicrobial drugs in food-producing animals increases the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dissemination of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed scenario (7.5 mg/kg, two doses 24 hours apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with the scenarios that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis indicates that bacterial populations were the most sensitive to drug conversion factors into plasma (ß), elimination of the drug from the colon (υ), fifty percent sensitive bacteria (P. multocida) killing effect (Ls50), fifty percent of bacteria (E. coli) above ECOFF killing effect (Cr50), and net drug transfer rate in the lung (γ) parameters.

2.
Sci Rep ; 14(1): 4920, 2024 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418677

RESUMEN

The food animal sector's use of antimicrobials is heavily critiqued for its role in allowing resistance to develop against critically important antimicrobials in human health. The WHO recommends using lower tier antimicrobials such as florfenicol for disease treatment. The primary objective of this study was to assess the differences in resistance profiles of enteric microbes following administration of florfenicol to steers using both FDA-approved dosing regimens and two different detection methods. Our hypothesis was that we would identify an increased prevalence of resistance in the steers administered the repeated, lower dose of florfenicol; additionally, we hypothesized resistance profiles would be similar between both detection methods. Twelve steers were administered either two intramuscular (20 mg/kg q 48 h; n = 6) or a single subcutaneous dose (40 mg/kg, n = 6). Fecal samples were collected for 38 days, and E. coli and Enterococcus were isolated and tested for resistance. Fecal samples were submitted for metagenomic sequencing analysis. Metagenomics revealed genes conferring resistance to aminoglycosides as the most abundant drug class. Most multidrug resistance genes contained phenicols. The genotypic and phenotypic patterns of resistance were not similar between drug classes. Observed increases in resistant isolates and relative abundance of resistance genes peaked after drug administration and returned to baseline by the end of the sampling period. The use of a "lower tier" antimicrobial, such as florfenicol, may cause an increased amount of resistance to critically important antimicrobials for a brief period, but these changes largely resolve by the end of the drug withdrawal period.


Asunto(s)
Microbioma Gastrointestinal , Tianfenicol , Tianfenicol/análogos & derivados , Animales , Humanos , Escherichia coli/genética , Microbioma Gastrointestinal/genética , Tianfenicol/farmacología , Antibacterianos/farmacología , Enterobacteriaceae , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana
3.
J Vet Intern Med ; 37(6): 2478-2481, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37855228

RESUMEN

Two sheep presented with acute tonic-clonic seizures, opisthotonos, absent pupillary light reflexes and abnormal vital signs within 18 hours after observed consumption of leaves from an ornamental shrub later identified as wintersweet (Chimonanthus praecox). Despite symptomatic treatment, both sheep died. Three other sheep that consumed the plant died after displaying similar clinical signs, resulting in 2 deaths the prior evening and 1 recovery the next morning. Gross necropsy and histologic findings were diagnostically inconclusive. Rumen contents tested positive for the alkaloid calycanthine, a centrally-acting convulsant known to be present in wintersweet. Case reports of calycanthine toxicity in ruminants are limited, with no detailed reports published in the United States. Calycanthine has been isolated from the seeds, flowers, and leaves of the plant. Wintersweet is part of the family Calycanthaceae that including 3 species native to North America, all of which pose a neurologic risk to ruminants if consumed.


Asunto(s)
Calycanthaceae , Ovinos , Animales , Flores , Hojas de la Planta , Rumiantes , América del Norte
4.
Pathogens ; 11(6)2022 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-35745532

RESUMEN

Campylobacter jejuni is commonly isolated on selective media following incubation at 37 °C or 42 °C, but the impact of these temperatures on genome variation remains unclear. Previously, Campylobacter selective enrichments from the feces of steers before and after ceftiofur treatment were plated on selective agar media and incubated at either 37 °C or 42 °C. Here, we analyzed the whole genome sequence of C. jejuni strains of the same multilocus sequence typing (MLST)-based sequence type (ST) and isolated from the same sample upon incubation at both temperatures. Four such strain pairs (one ST8221 and three ST8567) were analyzed using core genome and whole genome MLST (cgMLST, wgMLST). Among the 1970 wgMLST loci, 7-25 varied within each pair. In all but one of the pairs more (1.7-8.5 fold) new alleles were found at 42 °C. Most frameshift, nonsense, or start-loss mutations were also found at 42 °C. Variable loci CAMP0575, CAMP0912, and CAMP0913 in both STs may regularly respond to different temperatures. Furthermore, frameshifts in four variable loci in ST8567 occurred at multiple time points, suggesting a persistent impact of temperature. These findings suggest that the temperature of isolation may impact the sequence of several loci in C. jejuni from cattle.

5.
J Comp Pathol ; 189: 52-58, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34886986

RESUMEN

An adult alpaca (Vicugna pacos) with a history of colic and anorexia was euthanized because of failure to respond to treatment. Macroscopically, pale-tan, multifocal to coalescing, firm nodules and plaques markedly expanded the omentum, mesentery and the parietal and visceral peritoneum of multiple abdominal organs, especially the right oviduct and associated mesosalpinx. Abundant dark-red watery digesta were present in the duodenum and jejunum. Histological evaluation of the right oviduct, abdominal visceral nodules and plaques and mesenteric lymph nodes revealed transmural expansion and replacement by an epithelial malignant neoplasm, comprised of tubules and acini of ciliated columnar cells supported by abundant fibrous connective tissue. Both ovaries were histologically normal. On the basis of the ciliated morphology of the neoplastic cells, the focus on the proximal reproductive tract and the unremarkable ovaries, a reproductive tubal adenocarcinoma with carcinomatosis was diagnosed, with both the endometrium and oviduct considered as the tissues of origin. The prominent ciliated morphology of the neoplastic cells and the classification of human fallopian tube (oviduct) neoplasia lead us to propose oviductal adenocarcinoma with widespread carcinomatosis as the definitive diagnosis. The lamina propria of the small intestine was infiltrated segmentally by lymphocytes, plasma cells and neutrophils, and Clostridium perfringens with beta2 toxin production was identified by polymerase chain reaction in the small intestinal contents. To our knowledge, this is the first report of these two distinct diseases in an alpaca.


Asunto(s)
Adenocarcinoma , Camélidos del Nuevo Mundo , Enteritis , Neoplasias Peritoneales , Adenocarcinoma/veterinaria , Animales , Enteritis/veterinaria , Femenino , Neoplasias Peritoneales/veterinaria , Reacción en Cadena de la Polimerasa/veterinaria
6.
Pathogens ; 10(11)2021 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-34832635

RESUMEN

Widespread dissemination of extended-spectrum beta-lactamase (ESBL) Escherichia coli (E. coli) in animals, retail meats, and patients has been reported worldwide except for limited information on small ruminants. Our study focused on the genotypic characterization of ESBL E. coli from healthy sheep and their abattoir environment in North Carolina, USA. A total of 113 ESBL E. coli isolates from sheep (n = 65) and their abattoir environment (n = 48) were subjected to whole-genome sequencing (WGS). Bioinformatics tools were used to analyze the WGS data. Multiple CTX-M-type beta-lactamase genes were detected, namely blaCTX-M-1, blaCTX-M-14, blaCTX-M-15, blaCTX-M-27, blaCTX-M-32, blaCTX-M-55, and blaCTX-M-65. Other beta-lactamase genes detected included blaCMY-2, blaTEM-1A/B/C, and blaCARB-2. In addition, antimicrobial resistance (AMR) genes and/or point mutations that confer resistance to quinolones, aminoglycosides, phenicols, tetracyclines, macrolides, lincosamides, and folate-pathway antagonists were identified. The majority of the detected plasmids were shared between isolates from sheep and the abattoir environment. Sequence types were more clustered around seasonal sampling but dispersed across sample types. In conclusion, our study reported wide dissemination of ESBL E. coli in sheep and the abattoir environment and associated AMR genes, point mutations, and plasmids. This is the first comprehensive AMR and WGS report on ESBL E. coli from sheep and abattoir environments in the United States.

8.
J Vet Intern Med ; 35(6): 2933-2936, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34514646

RESUMEN

Limited knowledge exists regarding the use of lidocaine as a prokinetic in ruminants and camelids to treat gastrointestinal ileus. In this retrospective study, ruminant and camelid cases diagnosed with ileus and treated with a lidocaine constant rate of infusion were assessed for adverse reactions and medical outcomes. A review of medical records was performed to identify cases in which lidocaine was administered as a prokinetic. Ten cases were identified consisting of 8 cattle, 1 goat, and 1 alpaca. Nine animals improved with a lidocaine treatment. No adverse effects were reported during lidocaine administration. Nine animals were discharged, and 1 was euthanized.


Asunto(s)
Camélidos del Nuevo Mundo , Enfermedades de los Bovinos , Ileus , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Ileus/tratamiento farmacológico , Ileus/veterinaria , Infusiones Intravenosas/veterinaria , Lidocaína/uso terapéutico , Estudios Retrospectivos , Rumiantes
9.
Microorganisms ; 9(9)2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34576730

RESUMEN

In order to mitigate the food animal sector's role in the growing threat of antimicrobial resistance (AMR), the World Health Organization (WHO) suggests the use of lower tier antimicrobials, such as florfenicol. Florfenicol has two dosing schemes used to treat primarily bovine respiratory disease. In this study, the objective was to characterize the plasma and gastrointestinal pharmacokinetics of each dosing regimen and assess the effect of these dosing regimens on the prevalence of resistant indicator bacteria over time. Twelve steers underwent abdominal surgery to facilitate the placement of ultrafiltration probes within the lumen of the ileum and colon, as well as placement of an interstitial probe. Following surgery, cattle were dosed with either 20 mg/kg IM every 48 h of florfenicol given twice (n = 6) or a single, subcutaneous dose (40 mg/kg, n = 6). Plasma, interstitial fluid, gastrointestinal ultrafiltrate, and feces were collected. Pharmacokinetic analysis demonstrated high penetration of florfenicol within the gastrointestinal tract for both the high and low dose group (300%, 97%, respectively). There was no significant difference noted between dosing groups in proportion or persistence of phenotypically resistant bacterial isolates; however, the percent of resistant isolates was high throughout the study period. The recommendation for the use of a lower tier antimicrobial, such as florfenicol, may allow for the persistence of co-resistance for antibiotics of high regulatory concern.

10.
Front Vet Sci ; 8: 635800, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34422938

RESUMEN

Squamous cell carcinoma (SCC) is a common dermatological neoplasia found in large animal species. Treatment options, such as surgery and cryotherapy may be difficult or not feasible. Alternative therapies, such as immunomodulating drugs, can potentially be used for companion large animals. The hypothesis of the following retrospective study is: following multiple intravenous and intralesional injections of a mycobacterial cell wall stimulant (MCW) regression of SCC in equine, bovine and caprine patients will be observed. In this observational-retrospective case series, patients included are 2 bovine, 2 caprine and 3 equine patients. The medical records at two different teaching veterinary hospitals were searched for cases with a positive histopathological diagnosis of squamous cell carcinoma that were subsequently treated with MCW, as either the sole therapy, or in conjunction with other therapies. Seven cases were included in this retrospective study. The median duration of therapy was 56.5 days, with 3 of the 7 patients being euthanized. Significant complications were seen in 3/7 patients. Repeated injections of a MCW may lead to reduction in lesion size of SCC in some cases, but long-term resolution is unlikely and the risk of significant complications is high; due to limited sample size and the variety in species, it is difficult to conclude if MCW is an effective therapy for SCC.

11.
Microorganisms ; 9(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557120

RESUMEN

Bacterial resistance to ceftiofur raises health concerns due to ceftiofur's extensive veterinary usage and structural similarity with the human antibiotic ceftriaxone. Ceftiofur crystalline-free acid (CCFA) and ceftiofur hydrochloride (CHCL) are ceftiofur types used therapeutically in cattle, but their potential impacts on Campylobacter prevalence and antimicrobial resistance remain unclear. In this study two groups of steers were each treated with CCFA or CHCL. In vivo active drug concentrations were measured and fecal samples were analyzed for Campylobacter for up to 42 days post-treatment. Following administration, the colonic concentration of ceftiofur initially increased then dropped to pre-treatment levels by day 8. The estimated prevalence of Campylobacter spp. was significantly (p = 0.0009) higher during the first week after CCFA treatment than after CHCL treatment (81.3% vs. 45.2%). Campylobacter jejuni predominated overall, with other Campylobacter spp. mainly identified in the first week after CCFA treatment. No treatment impacts were noted on ceftiofur minimum inhibitory concentration (MIC) for C. jejuni (10-20 µg/mL). More C. jejuni genotypes were detected in CCFA-treated than CHCL-treated steers. These findings suggest that ceftiofur did not significantly impact Campylobacter prevalence or ceftiofur MIC. However, CHCL may be preferable due to the lower likelihood of temporary increases in Campylobacter prevalence.

12.
Clin Infect Dis ; 72(4): 710-715, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-32628748

RESUMEN

Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss 3 potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be extremely beneficial. Therefore, the option of conducting HCTs to accelerate SARS-CoV-2 vaccine development should be preserved. As HCTs require many months of preparation, we recommend an immediate effort to (1) establish guidelines for HCTs for COVID-19; (2) take the first steps toward HCTs, including preparing challenge virus and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs.


Asunto(s)
COVID-19 , SARS-CoV-2 , Vacunas contra la COVID-19 , Ensayos Clínicos como Asunto , Humanos , Pandemias
13.
PLoS One ; 15(1): e0228138, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32004337

RESUMEN

Antimicrobial drugs administered systemically may cause the emergence and dissemination of antimicrobial resistance among enteric bacteria. To develop logical, research-based recommendations for food animal veterinarians, we must understand how to maximize antimicrobial drug efficacy while minimizing risk of antimicrobial resistance. Our objective is to evaluate the effect of two approved dosing regimens of enrofloxacin (a single high dose or three low doses) on Escherichia coli in cattle. We look specifically at bacteria above and below the epidemiological cutoff (ECOFF), above which the bacteria are likely to have an acquired or mutational resistance to enrofloxacin. We developed a differential equation model for the antimicrobial drug concentrations in plasma and colon, and bacteria populations in the feces. The model was fit to animal data of drug concentrations in the plasma and colon obtained using ultrafiltration probes. Fecal E. coli counts and minimum inhibitory concentrations were measured for the week after receiving the antimicrobial drug. We predict that the antimicrobial susceptibility of the bacteria above the ECOFF pre-treatment strongly affects the composition of the bacteria following treatment. Faster removal of the antimicrobial drugs from the colon throughout the study leads to improved clearance of bacteria above the ECOFF in the low dose regimen. If we assume a fitness cost is associated with bacteria above the ECOFF, the increased fitness costs leads to reduction of bacteria above the ECOFF in the low dose study. These results suggest the initial E. coli susceptibility is a strong indicator of how steers respond to antimicrobial drug treatment.


Asunto(s)
Antibacterianos/farmacología , Enrofloxacina/farmacología , Escherichia coli/efectos de los fármacos , Modelos Estadísticos , Relación Dosis-Respuesta a Droga
14.
F1000Res ; 9: 1154, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33500777

RESUMEN

Accelerating the availability of COVID-19 vaccines is critical to preventing further waves and mitigating the impact on society. However, preparations for large-scale manufacturing, such as building production facilities, are typically delayed until a vaccine is proven safe and effective. This makes sense from a commercial perspective, but incurs great costs in terms of lives lost and damage to the economy. Several policy options are available to reduce this delay, all of which involve incentives or subsidies to invest in production facilities. We review existing approaches, then propose a novel alternative using "option-based guarantees" in which the government commits to paying a proportion of the manufacturer's preparation costs should the product turn out not to be viable. Counterintuitively, this "payment for failure" is appropriate because in the case of success, a company makes a profit from the product itself, and does not need additional money from the government. While other approaches have critical roles, we argue that option-based guarantees are the most promising approach to ensuring a rapid vaccine for COVID-19. Compared to the alternative approaches, they reduce both costs to the government and risk to the companies, while maintaining an incentive to produce a high-quality product quickly and at scale.


Asunto(s)
COVID-19/prevención & control , Industria Farmacéutica/economía , Vacunas/economía , Vacunas contra la COVID-19/economía , Costos y Análisis de Costo , Gobierno , Humanos
15.
PLoS One ; 14(10): e0223378, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31584976

RESUMEN

Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29-40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47-20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacocinética , Enfermedades de los Bovinos/microbiología , Cefalosporinas/química , Cefalosporinas/farmacocinética , Farmacorresistencia Bacteriana , Escherichia coli/efectos de los fármacos , Animales , Antibacterianos/administración & dosificación , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Cefalosporinas/administración & dosificación , Escherichia coli/clasificación , Escherichia coli/genética , Heces/microbiología , Pruebas de Sensibilidad Microbiana , Microbiota , ARN Ribosómico 16S/genética
16.
J Vet Intern Med ; 33(4): 1796-1806, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31134697

RESUMEN

BACKGROUND: Salmonellosis is a major cause of morbidity and mortality in neonatal calves, often occurring before preventative vaccines can be administered. HYPOTHESIS/OBJECTIVE: To evaluate the protective effect on calves of colostrum from cows vaccinated with a commercially available Salmonella Newport bacterin against a Salmonella Typhimurium challenge. ANIMALS: Twenty Holstein bull calves from a university dairy farm. METHODS: Nonrandomized placebo-controlled trial in which colostrum was harvested from 30 cows that received 2 doses of either Salmonella bacterin or saline before calving. Colostrum collected from each group was pooled and fed to 2 groups of 10 calves at birth. At approximately 2 weeks of age, calves were challenged with Salmonella Typhimurium. Clinical, hematologic, microbiological, and postmortem findings were compared between the 2 groups. RESULTS: No differences in mortality, clinical findings, hematology results, blood and fecal cultures, or necropsy findings between the 2 groups were observed. Vaccinated cows had higher colostral titers, and calves fed this colostrum had higher serum titers (mean difference, 0.429; mean [SE], 0.852 [0.02] for vaccinated versus 0.423 [0.02] for control calves). CONCLUSIONS AND CLINICAL IMPORTANCE: Transfer of colostral immunoglobulins from Salmonella enterica serotype Newport bacterin to neonatal calves was not sufficient to decrease mortality, clinical signs, sepsis, intestinal damage, or fecal shedding when exposed to a highly pathogenic Salmonella isolate. A large-scale randomized controlled clinical trial is needed to evaluate the efficacy of this bacterin when administered in the dry period for prevention of salmonellosis in neonatal calves.


Asunto(s)
Enfermedades de los Bovinos/prevención & control , Calostro , Salmonelosis Animal/prevención & control , Vacunas contra la Salmonella/administración & dosificación , Animales , Animales Recién Nacidos/inmunología , Vacunas Bacterianas/administración & dosificación , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Estudios de Cohortes , Femenino , Inmunidad Materno-Adquirida , Masculino , Salmonelosis Animal/inmunología , Salmonella enterica/inmunología , Salmonella typhimurium/fisiología , Vacunación/veterinaria
17.
Artículo en Inglés | MEDLINE | ID: mdl-30849550

RESUMEN

BACKGROUND & AIMS: The epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection. METHODS: The significance of C parvum-induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies. RESULTS: Immunoneutralization of IFN-λ2/3 in C parvum-infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum-induced loss of barrier function by decreasing paracellular permeability to sodium. CONCLUSIONS: These studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection.


Asunto(s)
Criptosporidiosis/inmunología , Cryptosporidium parvum/fisiología , Citocinas/genética , Mucosa Intestinal/inmunología , Regulación hacia Arriba , Animales , Línea Celular , Criptosporidiosis/genética , Criptosporidiosis/parasitología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Ratones , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos , Porcinos
18.
Front Microbiol ; 9: 2190, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30283418

RESUMEN

Objective: The intestinal concentrations of antimicrobial drugs that select for resistance in fecal bacteria of cattle are poorly understood. Our objective was to associate active drug concentrations in the intestine of steers with changes in the resistance profile and composition of the fecal microbiome. Methods: Steers were administered either a single dose (12.5 mg/kg) or 3 multiple doses (5 mg/kg) of enrofloxacin subcutaneously every 24 h. Enrofloxacin and ciprofloxacin concentrations in intestinal fluid were measured over 96 h, and the abundance and MIC of E. coli in culture and the composition of the fecal microbiota by 16S rRNA gene sequencing were assessed over 192 h after initial treatment. Results: Active drug concentrations in the ileum and colon exceeded plasma and interstitial fluid concentrations, but were largely eliminated by 48 h after the last dose. The concentration of E. coli in the feces significantly decreased during peak drug concentrations, but returned to baseline by 96 h in both groups. The median MIC of E. coli isolates increased for 24 h in the single dose group, and for 48 h in the multiple dose group. The median MIC was higher in the multiple dose group when compared to the single dose group starting 12 h after the initial dose. The diversity of the fecal microbiota did not change in either treatment group, and taxa-specific changes were primarily seen in phyla commonly associated with the rumen. Conclusions: Both dosing regimens of enrofloxacin achieve high concentrations in the intestinal lumen, and the rapid elimination mitigates long-term impacts on fecal E. coli resistance and the microbiota.

20.
J Am Vet Med Assoc ; 253(7): 907-917, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30211646

RESUMEN

OBJECTIVE To identify factors associated with strongyle infection and parasite reduction strategies associated with low strongyle fecal egg counts (FECs) in goats on farms in North Carolina. DESIGN Cross-sectional study. ANIMALS 631 adult goats on 52 farms in North Carolina. PROCEDURES Participating farms were visited to collect fecal samples from goats and administer a survey regarding goat, environmental, and management factors. The McMaster technique was used to determine strongyle FEC for each sample. Univariate followed by multivariate modeling was performed to identify factors associated with FEC at the farm and individual goat level. RESULTS Multivariate analysis controlling for several other factors and multiple comparisons revealed that farms on which no anthelmintic drugs had ever been used had the lowest mean FECs, compared with farms on which specific strategies for parasite control were used; no other variables were significant. For individual goat FEC, significant variables included goat breed, breed type, owner-defined purpose, daily dietary protein intake, and fecal coccidia score. In particular, companion goats (vs meat or dairy goats) had the lowest FECs. Higher dietary protein intake and coccidia scores were associated with higher FECs. Among females, goats that had kidded in the last 6 weeks had the highest FECs. CONCLUSIONS AND CLINICAL RELEVANCE Various factors were identified that appeared to influence the likelihood of strongyle infection in goats. The finding that farms with no history of anthelmintic use had the lowest mean FECs suggested that a focus on preventative measures could reduce the need for anthelmintic drugs and, by extension, lessen the opportunity for the development of anthelmintic resistance.


Asunto(s)
Enfermedades de las Cabras/epidemiología , Infecciones por Strongylida/veterinaria , Strongyloides/aislamiento & purificación , Animales , Estudios Transversales , Femenino , Enfermedades de las Cabras/parasitología , Cabras , Masculino , North Carolina/epidemiología , Recuento de Huevos de Parásitos/veterinaria , Prevalencia , Infecciones por Strongylida/epidemiología
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