Global Foot-and-Mouth Disease Research Update and Gap Analysis: 5 - Biotherapeutics and Disinfectants.

We assessed knowledge gaps in foot-and-mouth disease (FMD) research. Findings are reported in a series of papers, and in this article, we consider biotherapeutics and disinfectants. The study took the form of a literature review (2011-2015) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. While vaccines will remain the key immunological intervention used against FMD virus (FMDV) for the foreseeable future, it takes a few days for the immune system to respond to vaccination. In an outbreak situation, protection could potentially be provided during this period by the application of rapid, short-acting biotherapeutics, aiming either to stimulate a non-specific antiviral state in the animal or to specifically inhibit a part of the viral life cycle. Certain antiviral cytokines have been shown to promote rapid protection against FMD; however, the effects of different immune-modulators appear to vary across species in ways and for reasons that are not yet understood. Major barriers to the effective incorporation of biotherapeutics into control strategies are cost, limited understanding of their effect on subsequent immune responses to vaccines and uncertainty about their potential impact if used for disease containment. Recent research has highlighted the importance of environmental contamination in FMDV transmission. Effective disinfectants for FMDV have long been available, but research is being conducted to further develop methods for quantitatively evaluating their performance under field, or near-field, conditions. During outbreaks in South Korea in 2010 there was public concern about potential environmental contamination after the mass use of disinfectant and mass burial of culled stock; this should be considered during outbreak contingency planning.

Prediction of the energy content of tallgrass prairie hay.

Two experiments were conducted to describe the DE content of tallgrass prairie hay (TPH). In trial 1, steers (n = 13; 277 +/- 15 kg of BW) were used in a 13 x 4 Latin square experiment to measure the DE of 13 samples of TPH fed at 1.5% of BW daily (average feeding level = 0.7 x the maintenance energy requirement). Hays were harvested from a variety of locations in east-central Kansas and represented an array of harvest dates and storage methods. In trial 2, steers (n = 16; 261 + 17 kg of BW) were used in a randomized complete block experiment to assess the effects of TPH intake level on DE. Hay was fed at 1.3, 1.7, 2.1, or 2.5% of BW daily, which corresponded to 0.9, 1.4, 1.6, and 1.9 x the maintenance energy requirement. Steers in both trials were fed soybean meal in amounts calculated to provide ruminally degradable protein (RDP) equal to 11% of digestible OM intake. Hay samples were analyzed for ash, N, NDF, ADF, ADIN, NDIN, acid detergent-insoluble ash, lignin, monosaccharides, and alkali-labile phenolic acids. Chemical components related to DE (P < 0.2) were subjected to iterative regression analysis to predict the DE concentration of the diet. Iterations were ceased when the error mean square of the regression was optimized. At 0.7 x maintenance, the dietary DE concentration (Mcal/kg) was described by: DE = 0.13(CP) - 0.16(ADL) + 2.11 (R(2) = 0.73; S(y*x) = 0.13). Forage OM digestion decreased linearly (P < 0.01) as forage intake increased. Apparent dietary DE concentration decreased by 7.4% when intake was increased from 1 to 2 x maintenance. When RDP was adequate, chemical composition values were useful indicators of forage DE content in our study. Moreover, increased forage intake depressed GE digestion by steers, but ultimately increased total DE intake. Energy digestion varied with forage intake in a predictable manner between 1 and 2 x the maintenance feeding level.

Processing scavenged blood with a cell saver reduces cerebral lipid microembolization.

BACKGROUND: Microembolization during cardiopulmonary bypass (CPB) can be detected in the brain as lipid deposits that create small capillary and arteriolar dilations (SCADs) with ischemic injury and neuronal dysfunction. SCAD density is increased with the use of cardiotomy suction to scavenge shed blood. Our purpose was to determine whether various methods of processing shed blood during CPB decrease cerebral lipid microembolic burden. METHODS: After hypothermic CPB (70 minutes), brain tissue from two groups of mongrel dogs (28 to 35 kg) was examined for the presence of SCADs. In the arterial filter (AF) group (n = 12), shed blood was collected in a cardiotomy suction reservoir and reinfused through the arterial circuit. Three different arterial line filters (Pall LeukoGuard, Pall StatPrime, Bentley Duraflo) were used alone and in various combinations. In the cell saver (CS) group (n = 12), shed blood was collected in a cell saver with intermittent preocessing (Medtronic autoLog model) or a continuous-action cell saver (Fresenius Continuous Auto Transfusion System) and reinfused with and without leukocyte filtration through the CPB circuit. RESULTS: Mean SCAD density (SCAD/cm2) in the CS group was less than the AF group (11 +/- 3 vs 24 +/- 5, p = 0.02). There were no significant differences in SCAD density with leukocyte filtration or with the various arterial line filters. Mean SCAD density for the continuous-action cell saver was 8 +/- 2 versus 13 +/- 5 for the intermittent-action device. CONCLUSIONS: Use of a cell saver to scavenge shed blood during CPB decreases cerebral lipid microembolization.

Mucosal infection and vaccination against feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) infection is a naturally occurring lentiviral infection of cats which progresses to immunodeficiency in a manner strikingly similar to that observed in HIV infection in man. The rectal and cervico-vaginal mucosae are common routes of transmission of HIV and it has been shown that the gastrointestinal tract is an important site of HIV infection and primary pathology. Although biting is the principle mode of transmission for FIV, we have shown that it is possible to reliably infect cats via both the rectal and vaginal routes. Using a biotin-streptavidin linked immunoperoxidase technique we have detected FIV core and envelope proteins in the colonic follicle associated epithelial cells, cells within the lymphoid follice and occasional cells in the lamina propria. Further, in the intestine we have detected FIV RNA and proviral DNA in epithelial cells, colonic lymphoid aggregates and isolated lamina propria cells. We have studied a group of asymptotic cats which have been rectally infected with FIV for 1 year or longer and shown an increase in the number of lamina propria CD8+ cells and greater levels of IL-2, IL-6, IL-10 and gamma-IFN mRNA. Since these cats remained clinically healthy these results might suggest that both local antibody and class I restricted cytotoxic lymphocytes (CTLs) may play a role in control of viral replication. We have investigated a range of vaccination regimes for their ability to generate responses which would protect from rectal challenge with virulent virus. Cats have been immunized with whole virus (FIV-pet, FIV-GLA-8), V3, V3MAP or C2 with cholera toxin (CT), or Quil A based adjuvants via rectal, intra-nasal, parenteral or targeted lymph node routes, and challenged rectally with ten mucosal cat infectious doses (MCID) of FIV-GLA-8. We have shown that the adjuvant effects of cholera toxin and Quil A are not influenced by the route of delivery (intraperitoneal (i.p.) versus rectal) with CT more effective in stimulating humoral and Quil A more effective in stimulating cellular responses to FIV antigens. However we have shown that, quantitatively, CT is more effective when used as an adjuvant via the intra-nasal than the rectal route. Recently, we have begun to investigate if the promising results obtained with targeted lymph node (TLN) vaccination in monkeys could be reproduced in the cat. We have shown that TLN was more effective than rectal immunisation in stimulating both humoral and proliferative responses. In a preliminary study we have also been able to detect FIV specific CTLs and have observed protection from rectal challenge in four out of four cats.

Effects of ruminal administration of supplemental degradable intake protein and starch on utilization of low-quality warm-season grass hay by beef steers.

Hereford x Angus steers were used in a 13-treatment, four-period, incomplete Latin square design to examine the effects of starch and degradable intake protein (DIP) supplements on forage utilization and ruminal function. Steers were given ad libitum access to low-quality hay (4.9% CP) and were not supplemented (NS) or received different amounts of starch (cornstarch grits; 0, .15, and .3% of initial BW) and DIP (Na-caseinate; .03, .06, .09, and .12% of initial BW) administered via ruminal fistulae in a 3 x 4 factorial arrangement of treatments. Supplemented steers consumed more (P < .01) forage OM, total OM, NDF, and digestible OM (DOM) than NS steers. Forage OM, total OM, NDF, and DOM intakes increased linearly (P < .01) as the amount of supplemental DIP increased. The addition of starch to supplements linearly decreased ( P < .01) the intake of forage OM, NDF, and DOM. The digestion of DM, OM, and NDF increased linearly (P < .01) with supplemental DIP and decreased linearly (P < or = .06) with supplemental starch. Particulate and liquid passages generally increased with DIP; however, starch level influenced the nature of the response (P = .03 and .06, respectively). Similarly, ruminal acid detergent-insoluble ash content generally decreased as starch increased, but the effect was dependent on DIP level (P < .01). Supplementation increased (P < .01) ruminal NH3 and total VFA and decreased (P < .01) ruminal pH relative to NS. All treatments supported average pH values in a range (6.3 to 6.7) unlikely to inhibit fibrolytic bacteria. Ruminal NH3 concentration increased quadratically (P = .03) with DIP and decreased linearly (P = .02) with starch. As DIP increased, total VFA concentration increased linearly (P = .02). Providing supplemental DIP to steers fed low-quality forage increased OM intake and digestion, whereas addition of starch to supplements decreased forage intake and digestion.