Cesarean-derived Colostrum-deprived Pigs Research Articles

Prior infection with Bordetella bronchiseptica enhanced colonization but not disease with Streptococcus suis

Bordetella bronchiseptica and Streptococcus suis are widely distributed swine pathogens. B. bronchiseptica is a primary pathogen and causes atrophic rhinitis and bronchopneumonia. S. suis is a contributing agent to porcine respiratory disease complex and causes systemic diseases including arthritis, meningitis, polyserositis, and septicemia. Colonization with B. bronchiseptica has been associated with increased colonization by other pathogenic bacteria and increased disease severity with viral and bacterial pathogens. It has also been reported to predispose cesarean derived, colostrum deprived (CDCD) piglets to S. suis systemic disease. Here, we evaluated the role of B. bronchiseptica colonization on S. suis colonization, dissemination, and disease in one study using conventional pigs and another using CDCD pigs. Pigs were challenged with S. suis, B. bronchiseptica, or B. bronchiseptica followed by S. suis. Incidence of S. suis disease was not increased in either study for animals pre-inoculated with B. bronchiseptica. Nasal colonization with S. suis was increased in coinfected animals, while B. bronchiseptica was similar between mono- and co-infected animals. Although increased S. suis disease was not seen in coinfected pigs, there is evidence that B. bronchiseptica can increase colonization with S. suis, which may contribute to enhanced disease when animals are stressed or immunocompromised.

Pathogenesis of a novel porcine parainfluenza virus type 1 isolate in conventional and colostrum deprived/caesarean derived pigs

Two experimental challenge studies were conducted to evaluate the pathogenesis of a porcine parainfluenza virus type 1 (PPIV-1) isolate. Four-week-old conventional (CON) pigs were challenged in Study 1 and six-week-old caesarean derived/colostrum deprived (CDCD) pigs were challenged in Study 2. Results indicate that PPIV-1 shedding and replication occur in the upper and lower respiratory tracts of CON and CDCD pigs as detected by RT-qPCR and immunohistochemistry. Mild macroscopic lung lesions were observed in CON pigs but not in CDCD pigs. Microscopic lung lesions were mild and consisted of peribronchiolar lymphocytic cuffing and epithelial proliferation in CON and CDCD pigs. Serum neutralizing antibodies were detected in the CON and CDCD pigs by 14 and 7 days post inoculation, respectively. This study provides evidence that in spite of PPIV-1 infection and replication in challenged swine, significant clinical respiratory disease was not observed.

Administration of granulocyte-colony stimulating factor (G-CSF) to pigs results in a longer mean survival time after exposure to Streptococcus suis

The use of immunomodulators is a promising alternative to the use of antibiotics for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease. Previously we demonstrated a replication-defective adenovirus vector that expresses porcine granulocyte colony-stimulating factor (G-CSF) elicited a sustained neutrophilia, lasting nearly 3 weeks, which may be beneficial to prevent bacterial diseases during times of peak incidence. In a pilot study using the vectored G-CSF with a Caesarian-derived, colostrum-deprived (CDCD) pig model of Streptococcus suis disease, only 1 of 4 pigs given G-CSF developed disease, while 3 of 4 non-treated pigs developed Streptococcal disease. In a subsequent study using a larger number of pigs, although there was no difference in overall survival, there was a longer mean survival time in G-CSF treated pigs. S. suis infection is more severe in CDCD pigs than conventionally raised pigs, consequently results in the field may be superior to the ones reported in this study. Although there were positive effects from the use of G-CSF in this study, further research is needed to determine if improved clinical outcomes could be achieved under field conditions and whether the use of G-CSF in pigs to induce a sustained increase in circulating neutrophil numbers may be useful as an adjunct to antibiotics to diminish the severity of Streptococcal disease, especially during times of stress and pathogen exposure such as post-weaning.

Duration of immunity for an inactivated Mycoplasma hyorhinis vaccine in pigs

Mycoplasma hyorhinis (Mhr) is a pathogen of pigs causing polyserositis and polyarthritis. The most susceptible population are nursery pigs of approximately 7 weeks of age, although we have shown that clinical signs can persist into finishing aged animals after a late-nursery infection. We have previously demonstrated the efficacy of a novel inactivated Mhr vaccine for the reduction of lameness and polyserositis in caesarian-derived colostrum-deprived (CDCD) pigs vaccinated at 3 weeks and challenged with Mhr at 6 weeks of age. Here we evaluated the duration of immunity (DOI) of the same vaccine. Vaccine or placebo was administered to CDCD pigs at 3 weeks of age. Pigs were challenged with Mhr at either 10 weeks of age (=7 week DOI) or 13 weeks of age (=10 week DOI). In the 7 week DOI, vaccination provided significant reductions in lameness (p = 0.0018), arthritis (p = 0.0002), and pericarditis (p = 0.0312) versus the placebo control. In the 10 week DOI, a significant reduction in arthritis (p = 0.0320) was observed in the vaccine group as compared to the placebo group. Both vaccine groups showed a significant increase (p < 0.0001) in the post-challenge average daily gain (ADG), gaining 0.2 kg/day more than their respective placebo groups.

Age susceptibility of caesarian derived colostrum deprived pigs to Mycoplasma hyorhinis challenge

Mycoplasma hyorhinis (MHR) is a major cause of lameness, arthritis, and polyserositis among growing pigs. Reduced performance and culling due to MHR infection result in economic losses in swine production.We have previously developed an MHR challenge model in seven week-old CDCD pigs using cell-associated challenge material which results in both severe pericarditis and lameness. In this study we sequentially challenged CDCD pigs at seven, ten, thirteen, and sixteen weeks of age. Lameness was observed in >60% of the animals in the first three age groups but only 33% in the oldest age group. The number of animals with arthritis declined from 100% at seven weeks, to 56% at ten weeks and approximately 25% at both thirteen and sixteen weeks of age. Pericarditis was observed in 87% of the seven week challenge group, 28% in the ten week challenge group, 8% in the thirteen week challenge group and 4% in the sixteen week challenge group. All challenged groups showed a reduced average daily gain (ADG) compared to their age-matched non-challenged control groups. The largest disparity in ADG (1.2 lbs/day difference) was noted at thirteen weeks of age.Results of this study demonstrate that these animals were susceptible to MHR-associated lameness through sixteen weeks of age while susceptibility to MHR-associated polyserositis appeared to peak at seven weeks of age.

Markedly different immune responses and virus kinetics in littermates infected with porcine circovirus type 2 or porcine parvovirus type 1

Porcine parvovirus type 1 (PPV1) and porcine circovirus type 2 (PCV2) are small single-stranded DNA viruses with high prevalence in the global pig population. The aim of this study was to compare and contrast PCV2 and PPV1 infections in high-health status pigs and to describe PCV2 long-term infection dynamics. Six caesarian-derived colostrum-deprived pigs were randomly divided into two groups and were experimentally infected with PCV2 or PPV1 at 5 weeks of age. All pigs had detectable viremia by day (D) 3 post-infection. Pigs infected with PPV1 had a detectable INF-α response by D3 followed by a high IFN-γ response by D6. The PPV1 pigs developed antibodies against PPV1 by D6 resulting in decreasing virus titers until PPV1 DNA became undetectable from D28 until D42. In contrast, PCV2-infected pigs had no detectable INF-α or IFN-γ response after PCV2 infection. PCV2-infected pigs had no detectable anti-PCV2 humoral response until D49 and had a sustained high level of PCV2 DNA for the duration of the study. While PPV1-infected pigs were clinically normal, PCV2-infected pigs developed severe clinical illness including fatal systemic porcine circovirus associated disease (PCVAD) by D28, fatal enteric PCVAD by D56 and chronic PCVAD manifested as decreased weight gain and periods of diarrhea. Microscopically, all three PCV2-infected pigs had lymphoid lesions consistent with PCVAD and associated with low (chronic disease) to high (acute disease) levels of PCV2 antigen. Under the study conditions, there was a lack of early IFN-γ and INF-α activation followed by a delayed and low humoral immune response and persisting viremia with PCV2 infection. In contrast, PPV1-infected pigs had IFN-γ and INF-α activation and an effective immune response to the PPV1 infection.

Development of Polioencephalomyelitis in Cesarean-Derived Colostrum-Deprived Pigs Following Experimental Inoculation with Either Teschovirus A Serotype 2 or Serotype 11

Teschovirus encephalomyelitis is a sporadic disease associated with Teschovirus A (PTV) serotype 1 and, less frequently, other serotypes. In recent years, the number of cases submitted to the Iowa State University Veterinary Diagnostic Laboratory with a history of posterior paresis has increased. Submission histories from various regions of the United States suggest a trend for clinical disease to persist in herds and affect a wider age-range of pigs than historically reported. Polioencephalitis and/or myelitis was consistently present and PTV was detected in affected neural tissue by PCR in a portion of cases. Sequencing from two clinical cases identified PTV-2 and PTV-11. To assess neuropathogenicity of these isolates, 5-week-old cesarean derived and colostrum-deprived pigs were assigned to three groups: negative control (n = 4), PTV-2-inoculated (n = 7), and PTV-11-inoculated (n = 7). Three PTV-2-inoculated pigs developed mild incoordination of the hind limbs, one of which progressed to posterior ataxia. While all PTV-11-inoculated pigs showed severe neurological signs consistent with Teschovirus encephalomyelitis, no evidences of neurological signs were observed in sham-inoculated animals. All PTV-2- and PTV-11-inoculated pigs had microscopic lesions consistent with Teschovirus encephalomyelitis. To our knowledge, this is the first description of PTV-11 and experimental study demonstrating the neuropathogenicity of PTV-11 in the United States.

Anti-TNF-α therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs

Tumour necrosis factor-α (TNF-α) has been shown to play a role in many inflammatory conditions. Currently anti-TNF-α drugs (e.g. etanercept) are used in humans for treatment of autoimmune diseases. In this study we aimed to elucidate the role of TNF-α in the development of virus-endotoxin-induced respiratory disease. Twenty-two caesarean derived colostrum deprived pigs were used. Initially, the availability in the lungs and circulation, and possible clinical and inflammatory effects of etanercept alone were assessed in 4 pigs after intratracheal and intraperitoneal administration of 0.5 mg/per route/per pig. High anti-TNF-α activity was detected in bronchoalveolar lavage (BAL) fluids, peritoneal lavage fluids and serum of all animals for at least 8 h post-inoculation (HPI). No clinical symptoms, lung lesions, lung cell infiltration or induction of IFN-α, IL-1, IL-6, IL-12 and TNF-α in BAL were detected. Subsequently, the ability of etanercept to block porcine TNF-α and its effect on the above mentioned parameters and on lung virus titres were assessed in 8 pigs. They were inoculated intratracheally with porcine respiratory coronavirus (PRCV) followed by lipopolysaccharide (LPS) 24 h later. Etanercept was administered at the time of LPS inoculation via the same routes and dose as in the initial experiment. The parameters were compared with a control group ( n = 8), receiving only PRCV-LPS. Half of the animals from each group were euthanized at 4 and the rest at 8 h after LPS inoculation. TNF-α was completely neutralized in 3 of the 4 animals euthanized at 4 HPI and significantly lower than in the PRCV-LPS group at all times. No significant differences in disease severity, lung lesions, virus replication, lung cell infiltration or levels of IFN-α, IL-1, IL-6 and IL-12/IL-23 were observed between the two groups. Blocking of TNF-α alone was not sufficient to ameliorate disease in the PRCV-LPS model of respiratory disease, possibly due to the redundancy in the proinflammatory cytokine cascade, or the involvement of other unidentified disease mediators.

Clinical effects of experimental dual infections with porcine reproductive and respiratory syndrome virus followed by swine influenza virus in conventional and colostrum-deprived pigs.

Previous studies demonstrated that experimental dual infections of pigs with porcine reproductive and respiratory syndrome virus (PRRSV) followed by H1N1 influenza virus cause more severe disease and growth retardation than the respective single virus infections. Here three experiments were undertaken to better define the clinical impact of combined PRRSV‐H1N1 infections in conventional and caesarean‐derived colostrum‐deprived (CDCD) pigs. Groups of pigs were inoculated by aerosol with PRRSV followed by H1N1 at 3‐, 7‐ or 14‐day intervals. During the post‐H1N1 period, mean body temperatures, respiratory signs and mean weight gains in the PRRSV‐H1N1 inoculated groups were recorded and compared with those in uninoculated controls (experiments 1 and 2) or in singly virus‐inoculated pigs (experiment 3). In a first experiment with conventional pigs, the PRRSV‐3d‐H1N1 and PRRSV‐7d‐H1N1 infections induced mean body temperatures >40.5°C during 8 days (peaks 41.1 and 41.6°C, respectively) and mean growth reductions of 3.4 and 4.8 kg, respectively, during the 2 weeks after H1N1, along with marked depression and respiratory disease. The PRRSV‐14d‐H1N1 infection, on the contrary, was largely subclinical. In a second experiment with conventional pigs, PRRSV‐3d‐H1N1 and PRRSV‐7d‐H1N1 infections were clinically milder, with smaller increases in mean body temperatures (peak 40.5°C in both groups) and growth reductions (1.4 and 1.6 kg, respectively). In both groups, only one pig showed prominent general and respiratory signs. In a final experiment with CDCD pigs, PRRSV‐7d‐H1N1 infection had minimal effects on mean clinical performances and growth and, except for one pig that was severely affected, differences with the single virus inoculations were negligible. Thus, both the time interval between infections and the sanitary status of pigs can affect the clinical outcome of dual PRRSV‐H1N1 infections. However, factors so far unknown seem to cause large variations in the clinical response between individual pigs.

A potential role for tumour necrosis factor-alpha in synergy between porcine respiratory coronavirus and bacterial lipopolysaccharide in the induction of respiratory disease in pigs.

This study examined whether exposure of pigs to both porcine respiratory coronavirus (PRCV) and bacterial lipopolysaccharide (LPS) can potentiate respiratory disease and lung secretion of tumour necrosis factor-a (TNF-alpha) and interleukin-1 (IL-1). Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with PRCV, with LPS from Escherichia coli O111:B4 (20 microg/kg), or with a combination of the two, and killed at set times after inoculation. Clinical signs, virus replication and (histo)pathological changes in the lungs, percentage of neutrophils and bioactive TNF-alpha and IL-1 in broncho-alveolar lavage (BAL) fluids were examined. The effects of separate virus or LPS inoculations were subclinical and failed to induce high and sustained cytokine levels. In a preliminary study, pigs were inoculated with PRCV and then with LPS 24 h later and killed sequentially. Severe respiratory disease and significantly enhanced TNF-alpha titres (208-3601 U/ml versus 40-89 U/ml after LPS only) were seen during the first 12 h after LPS inoculation. IL-1 levels (106-1631 U/ml versus 28-654 U/ml after LPS only) were also increased, but persisted for longer after clinical recovery than TNF-alpha. In a second study, pigs were inoculated with PRCV and subsequently with LPS at various time intervals ranging from 0 to 24 h, and killed 5 h after inoculation with LPS. A time interval of at least 12 h between inoculations was necessary for prominent respiratory signs to develop. Production of TNF-alpha, but not IL-1, was also dependent on the time interval between inoculations and was tightly correlated with disease. Lung neutrophil infiltration and pathological changes were comparable after combined PRCV-LPS and single LPS inoculations, and were not associated with disease. These data show that exposure to high endotoxin concentrations in swine buildings can precipitate respiratory disease in PRCV-infected pigs, and that TNF-alpha is probably an important mediator of these effects. This is the first in-vivo demonstration of synergy between respiratory viruses and LPS.

Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity

The acute stages of infection with swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive-respiratory syndrome virus (PRRSV) were shown to differ in terms of clinical and lung inflammatory effects and proinflammatory cytokine profiles in bronchoalveolar lavage (BAL) fluids. Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with one of the three viruses.SIVinfection was followed within 1 day post inoculation (dPI) by characteristic respiratory and general signs, and excessive lung epithelial desquamation and neutrophil infiltration (38 to 56 per cent ofBALcells at 1 dPIvs 0 to 1 per cent in controls). High concentrations of bioactive interferon-α (IFN-α), tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) coincided with peak symptoms and neutrophil infiltration.PRCVinfection was asymptomatic and produced a mild bronchointerstitial pneumonitis and neutrophil infiltration (13 to 22 per cent ofBALcells at 4 dPI).IFN-α titres parallelled those found duringSIVinfection,TNF-α was negligible andIL-1 undetectable.PRRSVinfection induced anorexia and lethargy between 3 and 5 dPI. There was marked infiltration with mononuclear cells in alveolar septa andBALfluids between 7 and 10 dPI, while neutrophils remained at less than 11 per cent ofBALcells at any time.IL-1 was produced from three throughout 10 dPI, whileIFN-α production was minimal andTNF-α undetectable. These data strongly suggest that proinflammatory cytokines can be important mediators of viral respiratory disease.

Experimental reproduction of Haemophilus parasuis infection in swine: clinical, bacteriological, and morphologic findings.

Haemophilus parasuis is a common cause of polyserositis and polyarthritis in swine. Little is known about the mucosal and systemic sites of replication and lesions which follow an aerosol exposure to H. parasuis. In this experiment 5-week-old cesarean-derived, colostrum-deprived (CDCD) pigs were inoculated intranasally with an inoculum containing 2 x 10(9) colony-forming units of H. parasuis. Two principals and one control pig were necropsied at 12, 36, 84, and 108 hours postinoculation (PI) and samples obtained for bacteriologic culture and microscopic examination. Inoculated pigs developed clinical signs of inappetence, reluctance to move, lameness, and a serous nasal discharge. Macroscopic findings included a fibrinous polyserositis and polyarthritis 36 hours PI which became progressively more severe at 84 and 108 hours PI. No lung lesions were grossly visible. Microscopic lesions included a mild purulent rhinitis at each post inoculation interval and fibrinous to fibrinopurulent synovitis and serositis at 36, 84, and 108 hours PI. A focal suppurative bronchopneumonia was observed in one pig examined at 36 hours PI. The nasal cavity and trachea were the only mucosal sites from which H. parasuis was reisolated. Haemophilus parasuis was isolated from the blood and systemic sites at 36, 84, and 108 hours PI. Findings presented indicated that intranasal inoculation of 5-week-old CDCD pigs with H. parasuis results in clinical signs and lesions of polyserositis and polyarthritis typical of field cases and is a useful model for the study of H. parasuis pathogenesis. The results also suggest that H. parasuis initially colonizes the nasal mucosa.

Evaluation of killed and modified live porcine rotavirus vaccines in cesarean derived colostrum deprived pigs

Twenty-eight cesarean derived, colostrum deprived (CDCD) piglets were used to evaluate the efficacy of killed and modified live rotavirus (MLV) vaccines against challenge with virulent A-1 and A-2 rotaviruses. Two killed rotavirus vaccines were evaluated: an experimental vaccine and a commercially available vaccine. Efficacy parameters included: average daily weight gains, rotavirus shedding in feces, morbidity incidence and duration, and rotavirus serum antibody conversion post-vaccination and post-challenge. Piglets vaccinated orally/intramuscularly with the modified live vaccine were completely protected from A-1 and A-2 virulent rotavirus challenge. Nonvaccinated control piglets and piglets receiving killed rotavirus vaccines developed diarrhea, shed virus and exhibited reduced weight gains post-challenge. Only the MLV rotavirus vaccine was able to prevent virus shedding in feces after virulent challenge. Both controls and pigs which received killed vaccines intraperitoneally, orally or intramuscularly shed virus in the feces for 7 days post-challenge and virus peak titers approached 10 7 fluorescent antibody infectious dose (FAID) 50/g feces. These studies clearly reflected the inability of killed rotavirus vaccines to induce active local immunity to rotaviral diarrhea in piglets.