Efficacy, duration, and onset of immunogenicity of a West Nile virus vaccine, live Flavivirus chimera, in horses with a clinical disease challenge model

REASON FOR PERFORMING STUDY: West Nile virus (WNF) is a Flavivirus responsible for a life-threatening neurological disease in man and horses. Development of improved vaccines against Flavivirus infections is therefore important. OBJECTIVES: To establish that a single immunogenicity dose of live Flavivirus chimera (WN-FV) vaccine protects horses from the disease and it induces a protective immune response, and to determine the duration of the protective immunity. METHODS: Clinical signs were compared between vaccinated (VACC) and control (CTRL) horses after an intrathecal WNV challenge given at 10 or 28 days, or 12 months post vaccination. RESULTS: Challenge of horses in the immunogenicity study at Day 28 post vaccination resulted in severe clinical signs of WNV infection in 10/10 control (CTRL) compared to 1/20 vaccinated (VACC) horses (P<0.01). None of the VACC horses developed viraemia and minimal histopathology was noted. Duration of immunity (DPI) was established at 12 months post vaccination. Eight of 10 CTRL exhibited severe clinical signs of infection compared to 1 of 9 VACC horses (P<0.05). There was a significant reduction in the occurrence of viraemia and histopathology lesion in VACC horses relative to CTRL horses. Horses challenged at Day 10 post vaccination experienced moderate or severe clinical signs of WNV infection in 3/3 CTRL compared to 5/6 VACC horses (P<0.05). CONCLUSIONS: This novel WN-FV chimera vaccine generates a protective immune response to WNV infection in horses that is demonstrated 10 days after a single vaccination and lasts for up to one year. POTENTIAL RELEVANCE: This is the first USDA licensed equine WNV vaccine to utilise a severe challenge model that produces the same WNV disease observed under field conditions to obtain a label claim for prevention of viraemia and aid in the prevention of WNV disease and encephalitis with a duration of immunity of 12 months.     

Pigeon paramyxovirus: association with common avian pathogens in chickens and serologic survey in wild birds

Pigeon paramyxovirus-1 (PPMV-1) was isolated from pigeons from east-central Alabama and used in association with chicken anemia virus (CAV), infectious bursal disease virus (IBDV), or finch Mycoplasma gallisepticum (MG) in specific-pathogen-free chickens to assess dinical disease and pathology. PPMV-1 infection in all groups was conducted at day 10 of age via the ocular route. The low passage PPMV-1 isolate was inoculated into chickens in different groups at 10 days post-CAV infection, 6 days post-IBDV infection, and 6 days post-finch MG infection, respectively. Additionally, to obtain information on the status of paramyxovirus infection in the wild bird population of the region, we used a multispecies competitive enzyme-linked immunosorbent assay kit to assess serum samples from 180 wild birds representing 24 species obtained throughout 2001. Mild respiratory signs characterized by sneezing were observed in PPMV-1-infected chicks. In the brain, PPMV-1 caused disseminated vasculitis in the neuropile and meninges, sometimes with small foci of gliosis. Most brains had only mild lesions. In the upper respiratory tract, lesions were confined to the larynx and proximal trachea as hyperplasia of laryngeal mucosa-associated lymphoid tissue. In the lung, PPMV-1 caused minimal to moderate multifocal interstitial pneumonia. Lymphocytic expansion occurred in the interstitium of the Harderian gland. PPMV-1 in the spleen caused expansion of the white pulp as a result of hypertrophy of the macrophages in the periarteriolar sheaths accompanied by lymphocytic hyperplasia at the periphery. No severe aggravation of either signs or lesions could be attributed to any of the avian pathogens used in association with PPMV-1. The serologic survey in wild birds showed antibody levels that were considered negative or doubtful. Interestingly, significantly (P < 0.05) higher mean titers were observed during the months of October and November 2001, following closely multiple PPMV-1 episodes of mortality in wild collard doves in northwestern Florida.     

In vitro generation of mature neutrophils from canine Lin- bone marrow cells

The major goal of this work was to describe the in vitro generation of mature functional neutrophils derived from a canine enriched haematopoietic progenitor cell population. We have utilised lineage depletion by immunomagnetic selection to isolate a canine haematopoietic progenitor cell population. The physical, immunological, metabolical and morphological methodologies employed in this study have permitted us to isolate and define a cell population enriched in Rh-123low and CD34+ cells. Irradiated pre-established long-term bone marrow cultures (LTBMC) were utilised to determine the self-renewal ability of lineage negative (Lin-) cells, as well as their capacity to differentiate into mature functional neutrophils. The authors demonstrate for the first time that canine neutrophils derived from Lin- cells are able to produce oxyradicals, express a specific neutrophil surface antigen, and contain gelatinase granules. These characteristics enable them to migrate through basement membranes to act as a first line defence mechanism. The fact that these cells are able to differentiate into functional mature cells, and give rise to long-term culture-initiating cells (LTC-IC) after 35 days of culture, allows the authors to assure that the isolated canine enriched haematopoietic cell population exhibit functional characteristics, associated with primitive haematopoietic cells.     

Persistence of Salmonella Typhimurium DT120 in abattoir paddocks holding sheep

In the summer of 1999 there was an outbreak of Salmonella Typhimurium DT120 in people in the north of England which was unusual in being sensitive to antimicrobial drugs. The outbreak was linked to mutton and lamb from a local abattoir, and attention focused on four holding paddocks used to retain sheep before slaughter. In November 1999, samples of soil and faeces were taken from these paddocks and samples of faeces were taken from the concrete race leading from them. Salmonella Typhimurium was isolated from 59 of the 100 samples. Between January 2000 and October 2000 seven visits were made to the abattoir at each of which 100 samples were taken from the paddocks and concrete race and examined for the presence of Salmonella. The paddocks remained heavily contaminated with S Typhimurium DT120 until April when there was a marked reduction in the recovery of the organism. By June the contamination was minimal and by August it had disappeared, and the organism was not recovered in September or October.     

Subtotal pericardectomy and epicardial excision for treatment of coccidioidomycosis-induced effusive-constrictive pericarditis in dogs: 17 cases (1999-2003)

OBJECTIVE: To determine the history, clinicopathologic findings, and results of surgery for effusive-constrictive pericarditis associated with Coccidioides immitis infection in dogs. DESIGN: Retrospective study. ANIMALS: 17 client-owned dogs that underwent a subtotal pericardectomy and epicardial excision. PROCEDURE: Hospital records from May 1999 to June 2003 were reviewed. Data collected included history, clinicopathologic findings, treatments, and outcome. Follow-up information was obtained via recheck examination and by use of standardized telephone interviews with referring veterinarians and owners. RESULTS: All dogs were of large breeds, and most were male (mean age, 4.66 years). Ten dogs had no prior history of C. immitis infection, and 7 dogs had chronic infection with C. immitis. Having a chronic C. immitis infection reduced the odds of survival, compared with no previous infection. All dogs had clinical signs of right-sided heart failure. All dogs had serum titers (range, 1:8 to 1:256) for antibodies against C. immitis prior to surgery, and titers were not significantly associated with outcome. Predominant echocardiographic findings were thickened pericardium, reduced right ventricular filling, and pleural or pericardial effusion. All dogs underwent a subtotal pericardectomy and epicardial excision and had fibrosing pyogranulomatous pericarditis in biopsy specimens obtained during surgery. The perioperative mortality rate was 23.5%, and the 2-year postdischarge survival rate was 82%. CONCLUSIONS AND CLINICAL RELEVANCE: Surgical treatment via subtotal pericardectomy and epicardial excision is successful at relieving right-sided heart failure in dogs with effusive-constrictive pericarditis secondary to C. immitis infection, but long-term treatment with antifungal agents may still be required.     

Immunocompetence in organically fed finishing pigs: effect of corn cob mix

Two consecutive experiments were performed to evaluate the effects on the immune response of corn cob mix (CCM) in an organic pig diet. The immunoglobulin (Ig) M, IgA and IgG responses against an intramuscularly injected model antigen, bovine thyroglobulin, were used as indicator. The experiments were performed in an organic barn with nine pens of four crossbred pigs (two barrows and two sows) from 45 kg to slaughter. In the first experiment, the organic concentrate was mixed with organic CCM-silage to obtain three concentrate: CCM ratios of 100:0, 80:20 and 60:40 (w:w). In the second experiment, three concentrates were produced to obtain diets with equal nutrient levels on a dry matter basis after 0%, 20% and 40% CCM inclusion. Higher inclusion rates of CCM in the ration were accompanied by lower thyroglobulin-specific IgG responses. These effects could not be attributed to one specific component of the CCM, such as fatty acid composition, although there was a degree of correlation with lower vitamin A concentrations. Mycotoxin concentrations were absent or minimal. The study indicated that dietary ingredient composition may affect immunocompetence.     

Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies

OBJECTIVE: To evaluate genetic and metabolic predispositions and nutritional risk factors for development of pasture-associated laminitis in ponies. DESIGN: Observational cohort study. ANIMALS: 160 ponies. PROCEDURES: A previous diagnosis of laminitis was used to differentiate 54 ponies (PL group) from 106 nonlaminitic ponies (NL group). Pedigree analysis was used to determine a mode of inheritance for ponies with a previous diagnosis of laminitis. In early March, ponies were weighed and scored for body condition and basal venous blood samples were obtained. Plasma was analyzed for glucose, insulin, triglycerides, nonesterified fatty acids, and cortisol concentrations. Basal proxies for insulin sensitivity (reciprocal of the square root of insulin [RISQI]) and insulin secretory response (modified insulin-to-glucose ratio [MIRG]) were calculated. Observations were repeated in May, when some ponies had signs of clinical laminitis. RESULTS: A previous diagnosis of laminitis was consistent with the expected inheritance of a dominant major gene or genes with reduced penetrance. A prelaminitic metabolic profile was defined on the basis of body condition, plasma triglyceride concentration, RISQI, and MIRG. Meeting > or = 3 of these criteria differentiated PL- from NL-group ponies with a total predictive power of 78%. Determination of prelaminitic metabolic syndrome in March predicted 11 of 13 cases of clinical laminitis observed in May when pasture starch concentration was high. CONCLUSIONS AND CLINICAL RELEVANCE: Prelaminitic metabolic syndrome in apparently healthy ponies is comparable to metabolic syndromes in humans and is the first such set of risk factors to be supported by data in equids. Prelaminitic metabolic syndrome identifies ponies requiring special management, such as avoiding high starch intake that exacerbates insulin resistance.     

Estimation of the ideal ratio of true ileal digestible sulfur amino acids:lysine in 8- to 26-kg nursery pigs

Four experiments were conducted to determine the ideal ratio of true ileal digestible (TID) sulfur AA to Lys (SAA:LYS) in nursery pigs at two different BW ranges using both DL-Met and 2-hydroxy-4-(methylthio)-butanoic acid (HMTBA) as Met sources. In Exp. 1, 1,549 nursery pigs (Triumph 4 x PIC Camborough 22; initial BW 8.3 +/- 0.08 kg) were allotted to one of nine dietary treatments. The basal diet (Diet 1) was a semicomplex corn-soybean meal-based diet (1.32% TID Lys) with no supplemental HMTBA or DL-Met (47.7% TID SAA:LYS). Diets 2 to 9 consisted of the basal diet supplemented with four equimolar levels of DL-Met or HMTBA (52.7, 57.7, 62.7, and 67.7% TID SAA:LYS). In Exp. 2, 330 nursery pigs (Triumph 4 x PIC Camborough 22; initial BW 11.4 +/- 0.10 kg) were allotted to one of nine dietary treatments. The basal diet (Diet 1) was a corn-soybean meal-based diet (1.15% TID Lys) with no supplemental HMTBA or DL-Met (49% TID SAA:LYS). Diets 2 to 9 consisted of the basal diet supplemented with four equimolar levels of DL-Met or HMTBA (54, 59, 64, and 69% TID SAA:LYS). In Exp. 3, 1,544 nursery pigs (Triumph 4 x PIC Camborough 22; initial BW 12.4 +/- 0.13 kg) were allotted to one of nine dietary treatments as in Exp. 2. In Exp. 4, 343 nursery pigs (Genetiporc; initial BW 12.8 +/- 0.56 kg) were allotted to one of six dietary treatments. The basal diet (Diet 1) was a corn-soybean meal-based diet (1.05% TID Lys) with no supplemental DL-Met (49% TID SAA:LYS). Diets 2 to 5 consisted of the basal diet supplemented with four levels of DL-Met (54, 59, 64, and 69% TID SAA:LYS), and Diet 6 was the basal diet supplemented with one equimolar level of HMTBA to satisfy 59% TID SAA:LYS ratio. In all experiments, increasing the TID SAA:LYS ratio resulted in quadratic improvements in ADG (P < or = 0.09) and G:F (P < or = 0.05). Three different methods were used to estimate the optimal TID SAA:LYS ratio for each experiment. The two-slope broken-line regression model, x-intercept value of the broken-line and quadratic curve, and 95% of upper asymptote across the four experiments indicated that the average optimal TID SAA:LYS ratios were 59.3, 60.1, and 57.7% for ADG and 60.6, 61.7, and 60.1% for G:F, respectively. Thus, the optimal TID SAA:LYS ratio for 8- to 26-kg pigs based on the average value of these three estimates was 59.0% for ADG and 60.8% for G:F.