A Systematic Review and Meta-Analysis of Creep Feeding Effects on Piglet Pre- and Post-Weaning Performance.

In the present systematic review and meta-analysis, we evaluated the effects of providing piglets with creep feed during lactation on piglet pre- and post-weaning performance. A total of 20 articles met the inclusion criteria. Creep feeding in lactation improved pre-weaning piglet performance in 46% of the studies selected, while 58% of the included studies reported that creep feeding in lactation improved piglet performance during the nursery phase. Creep feeding increased the average piglet body weight (creep = 7.23 ± 0.30, no creep = 6.96 ± 0.31; p = 0.03) and litter weight (creep = 81.2 ± 4.18, no creep = 76.4 ± 4.22; p < 0.001) at weaning. The average piglet body weight and litter weight were positively associated (p < 0.001 and p < 0.001, respectively) with total creep feed intake. Creep feeding of piglets for more than 14 days increased (p = 0.003) the litter weight at weaning compared to litters not provided or provided for shorter periods with creep feed. The present work strengthened the notion that creep feeding during lactation presents opportunities for improving weaning weights and post-weaning piglet performance compared to litters not provided or provided for shorter periods with creep feed.

Testable Candidate Immune Correlates of Protection for Porcine Reproductive and Respiratory Syndrome Virus Vaccination.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an on-going problem for the worldwide pig industry. Commercial and experimental vaccinations often demonstrate reduced pathology and improved growth performance; however, specific immune correlates of protection (CoP) for PRRSV vaccination have not been quantified or even definitively postulated: proposing CoP for evaluation during vaccination and challenge studies will benefit our collective efforts towards achieving protective immunity. Applying the breadth of work on human diseases and CoP to PRRSV research, we advocate four hypotheses for peer review and evaluation as appropriate testable CoP: (i) effective class-switching to systemic IgG and mucosal IgA neutralizing antibodies is required for protective immunity; (ii) vaccination should induce virus-specific peripheral blood CD4+ T-cell proliferation and IFN-γ production with central memory and effector memory phenotypes; cytotoxic T-lymphocytes (CTL) proliferation and IFN-γ production with a CCR7- phenotype that should migrate to the lung; (iii) nursery, finishing, and adult pigs will have different CoP; (iv) neutralizing antibodies provide protection and are rather strain specific; T cells confer disease prevention/reduction and possess greater heterologous recognition. We believe proposing these four CoP for PRRSV can direct future vaccine design and improve vaccine candidate evaluation.

The importance of optimal body condition to maximise reproductive health and perinatal outcomes in pigs.

Overnutrition or undernutrition during all or part of the reproductive cycle predisposes sows to metabolic consequences and poor reproductive health which contributes to a decrease in sow longevity and an increase in perinatal mortality. This represents not only an economic problem for the pig industry but also results in poor animal welfare. To maximise profitability and increase sustainability in pig production, it is pivotal to provide researchers and practitioners with synthesised information about the repercussions of maternal obesity or malnutrition on reproductive health and perinatal outcomes, and to pinpoint currently available nutritional managements to keep sows' body condition in an optimal range. Thus, the present review summarises recent work on the consequences of maternal malnutrition and highlights new findings.

Heterologous vaccine immunogenicity, efficacy, and immune correlates of protection of a modified-live virus porcine reproductive and respiratory syndrome virus vaccine.

Although porcine reproductive and respiratory syndrome virus (PRRSV) vaccines have been available in North America for almost 30 years, many vaccines face a significant hurdle: they must provide cross-protection against the highly diverse PRRSV strains. This cross-protection, or heterologous vaccine efficacy, relies greatly on the vaccine's ability to induce a strong immune response against various strains-heterologous immunogenicity. Thus, this study investigated vaccine efficacy and immunogenicity of a modified live virus (MLV) against four heterologous type 2 PRRSV (PRRSV-2) strains. In this study, 60 pigs were divided into 10 groups. Half were MOCK-vaccinated, and the other half vaccinated with the Prevacent® PRRS MLV vaccine. Four weeks after vaccination, groups were challenged with either MOCK, or four PRRSV-2 strains from three different lineages-NC174 or NADC30 (both lineage 1), VR2332 (lineage 5), or NADC20 (lineage 8). Pre-and post-challenge, lung pathology, viral loads in both nasal swabs and sera, anti-PRRSV IgA/G, neutralizing antibodies, and the PRRSV-2 strain-specific T-cell response were evaluated. At necropsy, the lung samples were collected to assess viral loads, macroscopical and histopathological findings, and IgA levels in bronchoalveolar lavage. Lung lesions were only induced by NC174, NADC20, and NADC30; within these, vaccination resulted in lower gross and microscopic lung lesion scores of the NADC20 and NADC30 strains. All pigs became viremic and vaccinated pigs had decreased viremia upon challenge with NADC20, NADC30, and VR2332. Regarding vaccine immunogenicity, vaccination induced a strong systemic IgG response and boosted the post-challenge serum IgG levels for all strains. Furthermore, vaccination increased the number of animals with neutralizing antibodies against three of the four challenge strains-NADC20, NADC30, and VR2332. The heterologous T-cell response was also improved by vaccination: Not only did vaccination increase the induction of heterologous effector/memory CD4 T cells, but it also improved the heterologous CD4 and CD8 proliferative and/or IFN-γ response against all strains. Importantly, correlation analyses revealed that the (non-PRRSV strain-specific) serum IgG levels and the PRRSV strain-specific CD4 T-cell response were the best immune correlates of protection. Overall, the Prevacent elicited various degrees of efficacy and immunogenicity against four heterologous and phylogenetically distant strains of PRRSV-2.

Effects of farrowing induction with prostaglandins on farrowing traits and piglet performance: A systematic review and meta-analysis.

Induction of farrowing with prostaglandins is a way of increasing farrowing supervision and to provide adequate care for piglets in the first hours of life. However, some studies observed negative effects associated with induction, including decreased piglet viability, reduced birth weight and decreased colostrum yield. Furthermore, the farrowing response of sows to prostaglandins treatment varies among studies, largely influenced by the induction protocol applied. Thus, a systematic review and meta-analysis was carried out to evaluate the effects of farrowing induction with prostaglandins on stillbirth rate, birth weight, pre-weaning mortality, weaning weight, farrowing duration and colostrum and milk characteristics as well as the farrowing response to prostaglandin treatment. The interval from farrowing induction to onset of farrowing (IFIOF) was 31 h, and a twice application of prostaglandin increased by 37% the proportion of sows farrowing during the next working day. Prostaglandins had no effect on farrowing duration (P > 0.05). Piglet birth weight and weaning weight were only decreased (P < 0.05) when farrowing was induced ≥3 days before the expected farrowing date (based on herd average or in gestational length of the control group). Induction three or two days before the expected farrowing date had no effect on stillbirth rate; conversely, stillbirth rate was reduced by 28% (P < 0.05) when induction was performed one day before the expected farrowing date. Farrowing induction had no influence on pre-weaning mortality. The present study strengthened the observations that farrowing induction with prostaglandins is a valuable tool to reduce gestational length variation and to synchronize farrowing during the working day, allowing better assistance to sows and piglets. To obtain the maximum benefit of farrowing induction, it is recommended that induction should be performed one or two days before the expected farrowing date.

Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets.

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.

The Local and Systemic Humoral Immune Response Against Homologous and Heterologous Strains of the Type 2 Porcine Reproductive and Respiratory Syndrome Virus.

The humoral immune response plays a crucial role in the combat and protection against many pathogens including the economically most important, highly prevalent, and diverse pig pathogen PRRSV - the Porcine Reproductive and Respiratory Syndrome Virus. In addition to viremia and viral shedding analyses, this study followed the local and systemic humoral immune response of pigs for 63 days upon inoculation with one of three types of Type-2 PRRSV (PRRSV-2) strains - one modified live virus (MLV) vaccine strain, and two lineage 1 PRRSV-2 strains, NC134 and NC174. The local response was analyzed by quantifying immunoglobulin (Ig)A in nasal swabs. The systemic response was studied by the quantification of IgG with ELISA and homo- and heterologous neutralizing antibodies (NAs) utilizing a novel method of flow cytometry. In all PRRSV-2 inoculated groups, viral nasal shedding started at 3 dpi, peaked between 3 and 7 days post inoculation, and was cleared at 28-35 dpi with sporadic rebounds thereafter. The local IgA response started 4-7 days after viral shedding occurred and showed a bi-phasic course with peaks at 14 dpi and at 28-35 dpi. Of note, the NC134 and NC174 strains induced a much stronger local IgA response. As reported earlier, main viremia lasted from 7 dpi to 28 dpi (NC174), 42 dpi (NC134) or until the end of the study (MLV). Similar to the local IgA response, the systemic IgG response started 4-7 days after viremia; but in contrast to viremia, serum IgG levels stayed high for all PRRSV-2 inoculated groups until the end of the study. A significant finding was that while the serum NA response in the MLV group was delayed by 28 days, serum NAs in pigs infected with our two NC134 and NC174 strains could be detected as early as 7 dpi (NC134) and 14 dpi (NC174). Compared to homologous NA responses, the NA responses against heterologous strains was strong but slightly delayed between our lineage 1 one strains or non-existent between the MLV and lineage 1 strains. This study improves our understanding of the relationship between local and systemic infections and the humoral immune response induced by PRRSV-2 infection or MLV vaccination. Our data also provide novel insights into the timeline of the development of homologous and heterologous NA levels - by both MLV vaccination or infection with two strains from the currently prevalent PRRSV-2 lineage 1.

Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets.

Maternal-derived immunity is a critical component for the survival and success of offspring in pigs to protect from circulating pathogens such as Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study is to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (treatment (TRT) 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2 and 4 wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia, best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In the lungs, CD8 T cells were the primary and CD4 T cells were the secondary IFN-γ producers, including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets, and it introduces two novel immune cell subsets in pigs-IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

Effects of uterotonics on farrowing traits and piglet vitality: A systematic review and meta-analysis.

Uterotonics are widely used in the pig industry but their effects have not been investigated critically. The objective was to evaluate the effects of oxytocin and carbetocin on farrowing duration, birth interval, farrowing assistance, stillbirth rate, and piglet viability traits by performing a systematic review and a meta-analysis. The search for studies was performed during January 2020 using the PubMed, ISI Web of Science, Science Direct, and Scopus databases. The literature search was conducted using the key words: oxytocin, pig, farrowing, stillbirth, piglet, dose, and carbetocin. Studies which evaluated the effects of oxytocin or carbetocin on farrowing duration, birth interval, stillbirth rate, and farrowing assistance were included in the review. Of 1215 articles, 23 (1.9%) were selected for fulfilling the criteria for inclusion in the present study. A high variety of doses was observed among studies. Oxytocin increased (30%; P < 0.05) the stillborn proportion in the litters compared to control sows. Both oxytocin and carbetocin increased the need of farrowing assistance by 137% (P < 0.01) and 40% (P < 0.05), respectively, compared to control. The use of oxytocin reduced the farrowing duration by 18% and the birth interval by 17%, while carbetocin reduced the same responses by 27 and 23%, respectively (P < 0.01). When used judiciously, uterotonics are a valuable tool to shorten farrowing duration of hyperprolific sows. However, the treatment is not exempt of deleterious effects for piglets and sows. Therefore, the criteria to use these drugs should be based on individual cases and not as part of hormonal protocols for all parturient sows.

Comparative Plasma and Interstitial Fluid Pharmacokinetics of Meloxicam, Flunixin, and Ketoprofen in Neonatal Piglets.

Piglet castration and tail-docking are routinely performed in the United States without analgesia. Pain medications, predominately non-steroidal anti-inflammatory drugs, are used in the EU/Canada to decrease pain associated with processing and improve piglet welfare, however, past studies have shown the efficacy and required dose remain controversial, particularly for meloxicam. This study assessed the pharmacokinetics of three NSAIDs (meloxicam, flunixin, and ketoprofen) in piglets prior to undergoing routine castration and tail-docking. Five-day-old male piglets (8/group) received one of 3 randomized treatments; meloxicam (0.4 mg/kg), flunixin (2.2 mg/kg), ketoprofen (3.0 mg/kg). Two hours post-dose, piglets underwent processing. Drug concentrations were quantified in plasma and interstitial fluid (ISF) and pharmacokinetic parameters were generated by non-compartmental analysis. Time to peak concentration (Tmax) of meloxicam, flunixin, and S(-)-ketoprofen in plasma were 1.21, 0.85, and 0.59 h, compared to 2.81, 3.64, and 2.98 h in the ISF, respectively. The apparent terminal half-life of meloxicam, flunixin and S(-)-ketoprofen were 4.39, 7.69, and 3.50 h, compared to 11.26, 16.34, and 5.54 h, respectively in the ISF. If drug concentrations in the ISF are more closely related to efficacy than the plasma, then the delay between the Tmax in plasma and ISF may be relevant to the timing of castration in order to provide the greatest analgesic effect.

The T-Cell Response to Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV).

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous PRRSV strains. To improve PRRSV vaccine development, the aim of this study was to provide an in-depth analysis of the crucial heterologous T-cell response to type-2 PRRSV. Following PRRSV modified live virus (MLV) vaccination or infection using one high- or one low-pathogenic PRRSV-strain, this nine-week study evaluated the T-cell response to different PRRSV strains. Our results demonstrate an important role for T cells in this homo- and heterologous response. Specifically, the T-helper cells were the main responders during viremia. Their peak response at 28 dpi correlated with a reduction in viremia, and their homing receptor expression indicated the additional importance for the anti-PRRSV response in the lymphatic and lung tissue. The cytocoxic T lymphocyte (CTL) response was the strongest at the site of infection-the lung and bronchoalveolar lavage. The TCR-γδ T cells were the main responders post viremia and PRRSV induced their expression of the lymph node homing the chemokine receptor, CCR7: This indicates a crucial role for TCR-γδ T cells in the anti-PRRSV response in the lymphatic system.

Antibiotic Therapy Does Not Alter the Humoral Response to Vaccination for Porcine Circovirus 2 in Weaned Pigs.

Recent reports suggest that antibiotic therapy may either reduce or enhance the immune response to various porcine vaccines. Based upon these findings, we asked if antibiotic therapy alters immune cell populations, as measured by flow cytometry and/or vaccine-specific humoral immunity, as measured by sample to positive (S/P) antibody ratios. Here, we investigated the immuno-modulatory effects of enrofloxacin, ceftiofur, and tulathromycin on the immune response to a Mycoplasma hyopneumoniae (M. hyopneumoniae) and porcine circovirus type 2 (PCV-2) combination vaccine in weaned pigs. Maternal antibody likely interfered with the induction of immunity to M. hyopneumoniae. Antibiotic administration did not affect immune cell populations, as assessed by flow cytometry and did not affect the induction of humoral immunity to PCV-2.

Effects of post-insemination energy content of feed on embryonic survival in pigs: A systematic review.

The feeding of diets with greater energy content than that needed for body maintenance following mating is believed to reduce embryonic survival in pigs. In swine operations, therefore, feed intake is often restricted during the first and second week of pregnancy to reduce embryo mortality. There is thought to be a relationship between feeding diets that result in energy intake that is greater than that needed for body maintenance and embryonic death. This relationship is associated with lesser than typical progesterone (P4) concentrations when feeding diets with greater energy content due to increased hepatic clearance. There is no consensus, however, as to whether feeding should be restricted during early pregnancy to avert this possible detrimental effect. Thus, the aim of this systematic review is to assess the effect in sows and gilts of feeding diets with different energy contents post-mating on embryonic survival, evaluating when possible, the relationship of a greater energy intake and P4 concentrations on embryonic survival. An electronic search was conducted of the PubMed, Science Direct, Scopus, Web of science, and Scielo databases during June 2018. A total of 109 articles were retrieved, and of these, only 16 articles were selected after applying the selection criteria. There was no negative effect of a greater feed intake than that needed for body maintenance after breeding in 75% of the experiments. Results from 35% of the experiments indicated feeding early pregnant sows a diet with greater energy content than that needed for body maintenance resulted in augmented embryonic death. In 66.7% of the experiments, in which there was assessment of P4 concentration, there was no negative effect of feeding after farrowing a diet with greater energy than that needed for body maintenance. In conclusion, it appears that restricted feed intake in early pregnancy is no longer relevant when there are modern prolific dam lines utilized in swine production enterprises because dietary energy of as great as 54 MJ ME/day had no detrimental effect on embryo survival.

The Haemophilus ducreyi trimeric autotransporter adhesin DsrA protects against an experimental infection in the swine model of chancroid.

Adherence of pathogens to cellular targets is required to initiate most infections. Defining strategies that interfere with adhesion is therefore important for the development of preventative measures against infectious diseases. As an adhesin to host extracellular matrix proteins and human keratinocytes, the trimeric autotransporter adhesin DsrA, a proven virulence factor of the Gram-negative bacterium Haemophilus ducreyi, is a potential target for vaccine development. A recombinant form of the N-terminal passenger domain of DsrA from H. ducreyi class I strain 35000HP, termed rNT-DsrAI, was tested as a vaccine immunogen in the experimental swine model of H. ducreyi infection. Viable homologous H. ducreyi was not recovered from any animal receiving four doses of rNT-DsrAI administered with Freund's adjuvant at two-week intervals. Control pigs receiving adjuvant only were all infected. All animals receiving the rNT-DsrAI vaccine developed antibody endpoint titers between 3.5 and 5 logs. All rNT-DsrAI antisera bound the surface of the two H. ducreyi strains used to challenge immunized pigs. Purified anti-rNT-DsrAI IgG partially blocked binding of fibrinogen at the surface of viable H. ducreyi. Overall, immunization with the passenger domain of the trimeric autotransporter adhesin DsrA accelerated clearance of H. ducreyi in experimental lesions, possibly by interfering with fibrinogen binding.

Evaluation of factors important in modeling plasma concentrations of tetracycline hydrochloride administered in water in swine.

OBJECTIVE: To model the plasma tetracycline concentrations in swine (Sus scrofa domestica) treated with medication administered in water and determine the factors that contribute to the most accurate predictions of measured plasma drug concentrations. SAMPLE: Plasma tetracycline concentrations measured in blood samples from 3 populations of swine. PROCEDURES: Data from previous studies provided plasma tetracycline concentrations that were measured in blood samples collected from 1 swine population at 0, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 hours and from 2 swine populations at 0, 12, 24, 48, and 72 hours hours during administration of tetracycline hydrochloride dissolved in water. A 1-compartment pharmacostatistical model was used to analyze 5 potential covariate schemes and determine factors most important in predicting the plasma concentrations of tetracycline in swine. RESULTS: 2 models most accurately predicted the tetracycline plasma concentrations in the 3 populations of swine. Factors of importance were body weight or age of pig, ambient temperature, concentration of tetracycline in water, and water use per unit of time. CONCLUSIONS AND CLINICAL RELEVANCE: The factors found to be of importance, combined with knowledge of the individual pharmacokinetic and chemical properties of medications currently approved for administration in water, may be useful in more prudent administration of approved medications administered to swine. Factors found to be important in pharmacostatistical models may allow prediction of plasma concentrations of tetracycline or other commonly used medications administered in water. The ability to predict in vivo concentrations of medication in a population of food animals can be combined with bacterial minimum inhibitory concentrations to decrease the risk of developing antimicrobial resistance.

Passive immunization with a polyclonal antiserum to the hemoglobin receptor of Haemophilus ducreyi confers protection against a homologous challenge in the experimental swine model of chancroid.

Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme.

Evaluation of peripheral lymphocytes after weaning and vaccination for Mycoplasma hyopneumoniae.

This study evaluated immune cell populations in pigs following weaning and vaccination for Mycoplasma hyopneumoniae. Piglets (n=24) were weaned (day 0) at 16 (±1) days of age, and randomly assigned to the vaccination group (n=16) or control group (n=8). Complete blood cell counts, flow cytometry and serology were completed for blood samples collected on days 0 (within hours of weaning), 3, 7, 14, 30 and 60. The M. hyopneumoniae S:P ratios (sample optical density: positive control optical density) were negative in the vaccination group until days 30 and 60, when the S:P ratios were 1.3 and 1.0, respectively. Control animals remained serologically negative. The percentage of CD4(+) T cells was less (P<0.01) in control pigs than vaccinated pigs at day 3. In contrast, numbers of CD8(+) and CD4(+)CD8(+) T cells were greater (P<0.01) in control pigs than in vaccinated pigs at days 3 and 7. After day 7, few differences in immune cell types were evident between the groups. Differences in lymphocyte populations could not be solely attributed to vaccination, due at least in part, to the confounding influence of weaning. It was difficult to distinguish the influence of vaccination from the impact of weaning on peripheral immune cell populations.

Water-flow variation and pharmacoepidemiology of tetracycline hydrochloride administration via drinking water in swine finishing farms.

OBJECTIVE: To evaluate variation of drinking-water flow rates in swine finishing barns and the relationship between drinker flow rate and plasma tetracycline concentrations in pigs housed in different pens. DESIGN: Cross-sectional (phase 1) and cohort (phase 2) studies. SAMPLE POPULATION: 13 swine finishing farms (100 barns with 7,122 drinkers) in phase 1 and 100 finishing-stage pigs on 2 finishing farms (1 barn/farm) in phase 2. PROCEDURES: In phase 1, farms were evaluated for water-flow variation, taking into account the following variables: position of drinkers within the barn, type of drinker (swing or mounted), pig medication status, existence of designated sick pen, and existence of leakage from the waterline. In phase 2, blood samples were collected from 50 pigs/barn (40 healthy and 10 sick pigs) in 2 farms at 0, 4, 8, 24, 48, and 72 hours after initiation of water-administered tetracycline HCl (estimated dosage, 22 mg/kg [10 mg/lb]). Plasma tetracycline concentrations were measured via ultraperformance liquid chromatography. RESULTS: Mean farm drinker flow rates ranged from 1.44 to 2.77 L/min. Significant differences in flow rates existed according to drinker type and whether tetracycline was included in the water. Mean drinker flow rates and plasma tetracycline concentrations were significantly different between the 2 farms but were not different between healthy and sick pigs. The plasma tetracycline concentrations were typically < 0.3 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Many factors affected drinker flow rates and therefore the amount of medication pigs might have received. Medication of pigs with tetracycline through water as performed in this study had questionable therapeutic value.

Sulfamethazine water medication pharmacokinetics and contamination in a commercial pig production unit.

Sulfamethazine is often used to treat disease in the swine industry. Sulfamethazine is available as water or feed medication and historically (over the past 40 years) has been associated with residue violations in both the United States and Europe. Despite sulfamethazine's approval for use as a water medication, little research on the pharmacokinetics of the water formulation is available. Therefore, a pilot study was performed to determine the plasma levels of an approved sulfamethazine water medication. Plasma levels in pigs treated with an oral bolus (250 mg/kg), which is equivalent to the total drug consumed within a 24-h period, achieved therapeutic concentrations (50 microg/ml). Noncompartmental-based pharmacokinetic model parameters for clearance, half-life, and volume of distribution were consistent with previously published values in swine. However, the above treatment resulted in exposure of pen mates to sulfamethazine at levels currently above tolerance (0.1 ppm). Using a physiologically based pharmacokinetic model, the treatment dose simulation was compared with observed plasma levels of treated pigs. Flexibility of the physiologically based pharmacokinetic model also allowed simulation of control-pig plasma levels to estimate contamination exposure. A simulated exposure to 0.15 mg/kg twice within approximately 8 h resulted in detectable levels of sulfamethazine in the control pigs. After initial exposure, a much lower dose of 0.059 mg/kg maintained the contamination levels above tolerance for at least 3 days. These results are of concern for producers and veterinarians, because in commercial farms, the entire barn is often treated,and environmental contamination could result in residues of an unknown duration.