Evaluation of group vaccination of sows and gilts against Salmonella Typhimurium with an attenuated vaccine in subclinically infected pig herds.

Subclinical Salmonella Typhimurium infections occur frequently in pigs and constitute a major risk for human salmonellosis. With the currently available control measures, Salmonella Typhimurium infections in pigs remain difficult to control. Vaccination has been proposed to be an effective tool to control infections at farm level. In the current study, the effect of group vaccination of sows and gilts against Salmonella Typhimurium is evaluated on Salmonella prevalence in fecal and overshoe samples and ileocecal lymph nodes, and on serology in the sows and their offspring in three subclinically infected pig farms. In each farm, all sows and gilts were vaccinated twice, three weeks apart, with an attenuated histidine-adenine auxotrophic vaccine (Salmoporc®, IDT Biologika). From three months after the group vaccination onwards, all sows were given a booster dose three weeks before every farrowing. The farms were monitored bacteriologically and serologically from 12 months before until 15 months after the group vaccination. After group vaccination, no significant effect was detected in the prevalence of Salmonella Typhimurium in the fecal and overshoe samples collected in the sows (before: 2 %, after: 0 %) and their offspring at 18 weeks (before: 17 %, after: 11 %) and at 26 weeks of age (before: 15 %, after: 7 %), and when combining the results of the offspring at 18 and 26 weeks of age (before: 16 %, after: 9 %). Also, no significant effect was detected in the prevalence of Salmonella Typhimurium positive lymph nodes of sows (before and after: 0 %) and their offspring (before: 4 %, after: 7 %). Regarding serology, the mean S/P-ratios of the sows were significantly higher after the group vaccination, compared to before group vaccination (before: 1.50, after: 2.32, p < 0.001). The mean S/P-ratios of the offspring at slaughter age were significantly lower after the group vaccination, compared to before group vaccination (before: 1.71, after: 1.04, p = 0.001). In conclusion, group vaccination of sows and gilts resulted in a more beneficial serological status of the offspring, but did not significantly decrease Salmonella Typhimurium excretion and lymph node contamination.

Bacteriological evaluation of vaccination against Salmonella Typhimurium with an attenuated vaccine in subclinically infected pig herds.

Subclinical infections with Salmonella Typhimurium occur frequently in pigs. They constitute a risk for human salmonellosis and are difficult to control with currently available control measures. Vaccination against Salmonella Typhimurium in pigs can be an effective tool to control Salmonella infections at farm level. In the present study, the efficacy of an attenuated Salmonella Typhimurium vaccine (Salmoporc®, IDT Biologika) to control Salmonella infections in pigs was evaluated in three subclinically infected pig herds. The effect on Salmonella excretion and the number of pigs positive for Salmonella Typhimurium field and vaccine strains in ileocecal lymph nodes at slaughter were evaluated using five different vaccination strategies: 1. vaccination of sows, 2. vaccination of sows and piglets, 3. vaccination of sows and fattening pigs, 4. vaccination of piglets, 5. vaccination of fattening pigs, which were all compared to a non-vaccinated control group (experimental group 6). Each vaccination strategy was implemented in each farm, during two consecutive production cycles of the same sows. The prevalence of Salmonella Typhimurium field strain excretion was low; in total, 4% of the fecal and overshoe samples collected in the non-vaccinated control group were Salmonella Typhimurium field strain positive. The excretion of Salmonella Typhimurium field strain did not significantly differ between farms, production cycles and experimental groups. Applying vaccination in either sows and piglets, sows and fattening pigs, or in piglets only, resulted in a significantly reduced number of Salmonella Typhimurium field strain positive lymph nodes of slaughter pigs in the second production cycle, but not in the first production cycle. Vaccination of sows and piglets resulted in the most consistent reduction of Salmonella Typhimurium field strain positive lymph nodes at slaughter. The vaccine strain was detected in the lymph nodes of 13 pigs at slaughter, indicating the possible persistence of the vaccine strain until slaughter. Because of limitations in the study design, and the variability between farms and production cycles, the results of the current observational study should be extrapolated with care. Nevertheless, the results provide evidence that applying vaccination against Salmonella Typhimurium in sows and piglets (preferred), sows and fattening pigs, and piglets only can support the control of Salmonella Typhimurium infections by decreasing the prevalence of Salmonella Typhimurium field strain positive lymph nodes at slaughter.

Effects of attenuated vaccine protocols against Salmonella Typhimurium on Salmonella serology in subclinically infected pig herds.

Vaccination of pigs against Salmonella Typhimurium (S. Typhimurium) can be effective for the control of Salmonella infections at the farm level and reduce the risk of Salmonella contamination in the food chain. However, vaccination may interfere with herd serological status in serology-based Salmonella monitoring programs. The present study investigated the effects of an attenuated S. Typhimurium vaccine (Salmoporc, IDT Biologika) on Salmonella serology in sows, neonatal piglets and slaughter pigs from three subclinically infected herds. Within each herd, five different vaccination protocols were tested as follows: group 1, vaccination of sows; group 2, vaccination of sows and piglets; group 3, vaccination of sows and fattening pigs; group 4, vaccination of piglets; and group 5 vaccination of fattening pigs. Each group was compared to a non-vaccinated control group (group 6). Sera were analyzed by ELISA (HerdChek Swine Salmonella, IDEXX Laboratories) and sample-to-positive (S/P) ratios were calculated. At day 3 after farrowing, but not before vaccination, S/P ratios in vaccinated sows (mean: 2.21) were significantly higher than S/P ratios in non-vaccinated sows (mean: 0.87, P<0.001). S/P ratios in 3-day old piglets from vaccinated sows (mean: 2.46) were significantly higher than S/P ratios in similar piglets from non-vaccinated sows (mean: 0.73, P<0.001). At slaughter, S/P ratios in pigs from groups 2, 3, 4 and 5 were significantly higher than those in the non-vaccinated control group (P<0.001). Therefore, vaccination of piglets and fattening pigs could have implications for current serology-based Salmonella monitoring programs in slaughter pigs.

Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial.

BACKGROUND: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046). RESULTS: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

Preparation of microcapsules for skin allergy testing by the solvent evaporation process.

Polyurethanes and polyvinyl alcohol modified by stearyl isocyanate are used as a matrix for microparticles made by a solvent evaporation process to encapsulate allergenic molecules, with petrolatum used as a neutral vehicle. The encapsulation yields, depending on the agent to be encapsulated, vary from 22 to 45%.

Design of a potent and orally active nonpeptide platelet fibrinogen receptor (GPIIb/IIIa) antagonist.

The direct design of the potent nonpeptide platelet fibrinogen receptor (GPIIb/IIIa) antagonist, 8-[[[4- (aminoiminomethyl)phenyl]amino]carbonyl]-2,3,4,5-tetrahydro-3-oxo- 4- (2-phenylethyl)-1H-1,4-benzodiazepine-2-acetic acid, (3) (SB 207448), based on the structure and conformation of the potent and highly constrained cyclic peptide antagonist SK&F 107260 (2), has been reported [Ku et al., J. Am. Chem. Soc. 1993, 115, 8861]. While 3 displayed in vivo activity in the conscious dog following intravenous administration, it was not active following intraduodenal administration; activity was measured with an ex vivo platelet aggregation assay. The secondary amide in 3 was N-methylated in the expectation of increased absorption and bioavailability. The resulting tertiary amide, 4 (SB 208651), also showed high binding affinity for human GPIIb/IIIa and potent antiaggregatory activity in human platelet-rich plasma. Most importantly, 4 was active in vivo following intravenous and intraduodenal administration. Comparison of the iv and id inhibition curves suggests an apparent bioavailability of approximately 10%. Thus, 4 represents the first orally active compound in this series of potent, nonpeptide fibrinogen receptor antagonists.