Natural human interferon-alpha administered orally as a treatment of bovine respiratory disease complex.

Natural human interferon-alpha (nHuIFN-alpha) from three sources was given orally to 368 calves experiencing a natural outbreak of bovine respiratory disease complex (BRDC). In one study, 200 calves were given one treatment daily for 3 days of placebo or 20, 200, or 2,000 IU of nHuIFN-alpha before shipment. Calves treated with 20 or 200 IU had a significant (p < 0.05) weight gain benefit for the first 21 days in the feedlot, if they had rectal temperatures <40 degrees C when treated with nHuIFN-alpha. In a second trial, 168 mixed-breed calves (five groups randomized to 31-36 calves/group) were treated with one dose of placebo or 200 or 400 IU of nHuIFN-alpha after shipment to the feedlot. Using this regimen, a dose of 200 IU per calf significantly (p < 0.08) decreased the number of sick calves per group and delayed development of BRDC. Results of these studies demonstrate that oral administration of nHuIFN-alpha, which may partially mimic the nasally secreted IFN response reported during BRDC, may be beneficial in cattle.

Low dose oral interferon alpha 2a in HIV-1 seropositive patients: a double-blind, placebo-controlled trial.

Low dose oral interferon alpha has been shown to be of benefit in viral disease in animals. In a double-blind, placebo-controlled trial, 177 patients seropositive for HIV-1 were randomly assigned to receive placebo or recombinant human interferon alpha 2a (rIFN alpha). Endpoints were survival, alteration of disease classification, performance, and changes in CD4+ T cell numbers. There was a trend for improved survival in the group receiving rIFN alpha at the dose of 1.0 IU/lb. The changes in disease classification or in weight were not significantly different. Performance was improved to a greater extent (p=0.1) in the patients who received the two higher rIFN alpha dosages (1.0 IU/lb and 10.0 IU/lb) at 6 months. In addition, the CD4+ T cell count was improved only in the 1.0 IU/lb dose treatment group at 6 months. Treatment with low dose oral interferon at 1.0 IU/lb was associated with improved CD4+ T cell count, performance and a trend toward enhanced survival in HIV seropositive patients. These differences were, however, not statistically significant. A larger study, with better return rate, will be needed to determine whether low dose, oral interferon alpha is actually beneficial for these patients.

Oral treatment of transmissible gastroenteritis with natural human interferon alpha: a field study.

During a natural outbreak of transmissible gastroenteritis (TGE), groups of piglets were treated orally for 4 consecutive days with placebo or 1.0, 10.0 or 20.0 international units (IU) natural human interferon alpha (nHuIFN alpha). Piglets that were 1-12 days of age and given 1.0, 10.0 or 20.0 IU nHuIFN alpha had significantly (P < 0.01) greater survival rates than placebo-treated piglets; survival rates were the greater for the highest level of nHuIFN alpha treatment. In contrast, beneficial effects of nHuIFN alpha were not observed in piglets farrowed during the disease outbreak and given nHuIFN alpha within hours of birth. Oral nHuIFN alpha therapy modulates the natural course of high morbidity and mortality commonly seen with TGE.

Recovery rate and plasma zinc and copper concentrations of steer calves fed organic and inorganic zinc and manganese sources with or without injectable copper and challenged with infectious bovine rhinotracheitis virus.

Two experiments were conducted using feeder calves in a randomized block design to determine the effects of organic and inorganic sources of Zn and Mn fed pre- and posttransit (Exp. 1 and 2) with or without injectable Cu (Exp. 2) on DMI, rectal temperature, BW changes, and plasma Zn and Cu concentrations of feedlot steers challenged with infectious bovine rhinotracheitis virus (IBRV). In Exp. 1, before weaning, all steers and their dams received the following free-choice mineral supplements: 1) control (no supplemental Zn or Mn), 2) ZnO+MnO (ZnMnO), and 3) Zn methionine+Mn methionine (ZnMnMet). In Exp. 2, 18 d before weaning and shipping, steers were allotted into two groups (22 steers/group) and fed 225 mg of Zn.steer-1 x d-1 in .9 kg of ground corn as ZnO or ZnMet. Half of the steers from each group were injected (s.c.) with 120 mg of Cu from Cu glycinate. Steers (Exp. 1 and 2) were weaned and shipped approximately 2,500 km to the feedlot, where they received the same supplements in the form of a complete diet for 34 d, during which time calves recovered from the stress due to shipment. All steers were initially sero-negative to IBRV. On d 34 (d 0 of IBRV), all steers were challenged with IBRV and DMI, rectal temperature, and BW change were monitored for 28 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral therapy with human interferon alpha in calves experimentally injected with infectious bovine rhinotracheitis virus.

Fifty-six calves, seronegative for infectious bovine rhinotracheitis (IBR) virus, were randomly divided into 7 equal groups (n = 8) and given 0.0, 0.05, 0.50, or 5.00 international units (IU) of natural or recombinant human interferon alpha per kg body weight (nHuIFN-alpha or rHuIFN-alpha, respectively) orally once daily for 4 consecutive days, starting 2 days before intranasal inoculation with virulent IBR virus. Calves given 0.05 IU nHuIFN-alpha/kg bwt had significantly greater weight gain at days 15 (P < 0.10) and 25 (P < 0.05) than the placebo-treated (0.0 IU) control group. The treatment groups given 0.05 and 0.5 IU nHuIFN-alpha/kg bwt nHuIFN-alpha had fewer days with temperature > 40 degrees C (P < 0.05 and P = 0.10, respectively), and lower mean rectal temperatures on days 8 and 11 (0.05 IU/kg bwt; P < 0.10) or on day 11 (0.5 IU/kg bwt; P < 0.10). None of the calves given 0.05 IU nHuIFN-alpha/kg bwt required antibiotic therapy. Calves given 0.50 IU/kg bwt of nHuIFN-alpha, or 0.05 IU/kg bwt of rHuIFN-alpha had fewer (P < 0.05) total days of antibiotic therapy compared to controls. These data indicate that low dose oral IFN-alpha treatment significantly reduced the clinical effects of IBR virus infection in feedlot cattle in an interferon dose-dependent fashion.

The effect of low dose oral human interferon alpha therapy on diarrhea in veal calves.

Low doses of recombinant human interferon alfa 2a (rHuIFN-alpha 2a), were given orally in milk replacer formula to veal calves to determine the efficacy of rHuIFN-alpha 2a for protection against diarrhea, ear and/or respiratory tract infections common in vealing operations. Calves given rHuIFN-alpha 2a had fewer days and a lower incidence of diarrhea, compared to placebo-treated calves. Calves treated with rHuIFN-alpha 2a had significantly (P < 0.05) fewer ear infections and fewer total days of ear infection than did placebo-treated calves. The mortality rate was lower in the rHuIFN-alpha 2a treatment group (1.6%) than in the placebo treatment group (2.9%) and calves given rHuIFN-alpha 2a had a greater average weight gain (13.1 lbs. more per calf) than calves given placebo. These data demonstrate that orally administered rHuIFN-alpha 2a exhibited a protective effect against clinically significant signs of disease in veal calves, reduced the mortality rate in this population, and enhanced average weight gain.

The use of interferon modulates the negative effects of heat stress on poultry production.

A trial was conducted with broilers reared in two temperature environments; one was thermoneutral and the other had cycling ambient temperatures. Human interferon alpha (HuIFN-alpha) was added to the drinking water daily at four dose levels (0.0, 0.01, 0.1 and 1.0 international units (IU) per ml of drinking water). The trial began with 21 day old chicks housed either in a thermoneutral (24 degrees C) or a cycling ambient temperature (24-36 degrees C) environment. Interferon added to water at the highest concentration (1.0 IU/ml) improved surviability of birds in the cycling ambient temperature (24-36 degrees C) environment (P < 0.05). Birds housed in the cycling (24-36 degrees C) environment, drinking the lowest concentration of IFN-alpha 0.01 IU/ml, had a significantly improved weight gain-to-feed ratio. Oral IFN-alpha reduced the cost of production for birds reared in a cycling ambient temperature environment.

Type-I interferon genotypes and severity of clinical disease in cattle inoculated with bovine herpesvirus 1.

Genomic DNA samples and health records from 98 unrelated, mixed-breed cattle inoculated with bovine herpesvirus 1 (BHV-1) were examined to determine the relationship between interferon (IFN) genotype and severity of clinical disease. Cattle were retrospectively classified as moderately or severely affected on the basis of rectal temperature, feed intake, and weight gain after intranasal inoculation of BHV-1. Southern blot analysis of 16 type-I IFN genes identified alleles at 3 IFN loci (IFNB1, IFNW4, and IFNW8) that were significantly associated with the more severe clinical phenotype (odds ratios = 4.1 [P = 0.01], 2.3 [P < 0.05] and 2.4 [P = 0.06], respectively). A second allele at the IFNB1 locus was associated with the milder disease phenotype (odds ratio = 2.9, P < 0.05). These results indicate that selective breeding programs aimed at altering the frequency of these alleles in cattle populations may potentially improve animal health and lessen the economic impact of BHV-1 infection on cattle producers.

Influence of yeast culture on feeder calves and lambs.

Four experiments were conducted to determine the influence of yeast culture on 1) the health and performance of feeder calves, 2) the response of calves to an infectious bovine rhinotracheitis virus (IBRV) infection, and 3) nutrient utilization in lambs fasted for 3 d. In Exp. 1, 108 feeder calves were transported from Tennessee to Texas (1,600 km) and fed receiving diets containing 0 or .75% yeast culture and .35 or .69% P in a 2 x 2 factorial arrangement of treatments. In Exp. 2, 101 calves were transported 950 kg from Austin, TX to Bushland, TX and fed receiving diets containing 0, .75, 1.125, or 1.5% yeast culture. Yeast culture did not significantly affect the health or performance of calves in either experiment, although morbid calves fed yeast culture required fewer (P less than .05) days of antibiotic therapy in Exp. 2. In Exp. 3, feeder steers were fed diets containing 0 or .75% yeast culture and challenged intranasally with IBRV. Calves fed yeast culture tended to maintain heavier weights and higher DMI during IBRV infection than did steers fed the control diet. In Exp. 4, feeder lambs were fasted for 3 d and refed diets containing 0, .75, 1.125, or 1.5% yeast culture during a N and mineral balance trial. Lambs fed yeast culture had greater (P less than .08) N balance and tended to have greater Zn and Fe balance than control lambs. Results of these studies are interpreted to suggest that supplementation of morbid calves with yeast culture can have beneficial effects (fewer sick days, higher feed intakes) and that these effects may be mediated by improved N, Zn, and Fe metabolism.

Feed intake, rectal temperature, and serum mineral concentrations of feedlot cattle fed zinc oxide or zinc methionine and challenged with infectious bovine rhinotracheitis virus.

Three experiments were conducted using feedlot steers in a randomized block design to determine the effect of zinc methionine (ZnMet) and zinc oxide (Exp. 3) on feed intake (DMI), rectal temperature, and serum mineral concentrations of feedlot cattle challenged with infectious bovine rhinotracheitis virus (IBRV). All the steers used were seronegative to IBRV. Steers were adapted for 7 d to their respective diets and challenged with 3.7 x 10(5) plaque forming units of IRBV on d 0 of each experiment. Live BW, rectal temperature, and individual daily DMI were recorded for 14 d. Blood samples were taken on d 0, 7, and 14. In Exp. 1, daily DMI of the control steers (Zn = 31 ppm) decreased 50% compared with 15% in the ZnMet (Zn = 90 ppm) steers 3 d after IBRV challenge. By d 6, the ZnMet steers had regained their pretrial mean daily DMI, but the control steers took 11 d. The ZnMet steers had lower (P less than .05) mean rectal temperature than the control steers on d 7 and 12. In Exp. 2, the control (Zn = 35 ppm) steers had lower (P less than .05) daily DMI on d 8 to 12 than the ZnMet (Zn = 89 ppm) steers. In Exp. 3, the mean decrease in daily DMI tended to be more rapid in the ZnO steers than in the control and ZnMet steers. All steers had the lowest daily DMI on d 5 and 6, coinciding with the highest rectal temperature. Serum Zn, P, and Mg concentrations decreased and serum Cu increased in all steers after infection. These data suggest that dietary Zn enhanced the recovery rate of IBRV-stressed cattle.

Nutritional and dietary interrelationships with diseases of grazing beef cattle.

This article describes current methods of controlling acute bovine pulmonary emphysema (ABPEE) and edema, lungworm and gastrointestinal nematodes, and bloat in grazing beef cattle. Success in handling outbreaks of these conditions and in their prevention depends on an understanding of their epidemiology and pathogenesis. Supplementation with ionophore antibiotics is effective in prevention of ABPEE and bloat and may also prevent other diseases of cattle that graze lush pastures.

Influence of dietary protein concentrations on performance and nitrogen repletion in stressed calves.

Three trials were conducted to determine the influence of dietary CP concentration on health and performance of market-transport-stressed feeder calves (Exp. 1 and 2) and on repletion of nutrients lost during a 3-d feed and water deprivation period in steers fed at maintenance energy intake (Exp. 3). In Exp. 1 (84 calves) and 2 (256 calves), feeder calves averaging 184 kg were transported from Tennessee to Texas. In Exp. 1, calves were fed receiving diets containing either 12 or 16% CP. In Exp. 2, calves were fed diets containing 12 or 16% CP and .8 or 1.3% potassium in a 2 x 2 factorial arrangement of treatments. In Exp. 3, four Hereford steers averaging 253 kg were used in an N balance trial. Steers were deprived of feed and water for 3 d and then were limit-fed (1 x maintenance energy requirements) diets calculated to meet 100, 120, 140 or 160% of CP maintenance requirements for 14 d in a 4 x 4 Latin square design. In Exp. 1, calves fed the 16% CP diet had faster (P less than .05) daily gains and higher (P less than .10) feed consumption than calves fed the 12% CP diet during the first 14 d. In Exp. 2, calf performance was not affected by diet CP or K content. Calves fed the 16CP-1.3K diet had lower (P less than .10) mortality than calves on the remaining treatments. In Exp. 3, N balance and serum urea N increased linearly (P less than .05) with increasing dietary CP. Results of these studies are interpreted to indicate that the CP requirement (g/d) of market-transport-stressed feeder calves is similar to requirements of nonstressed calves; however, the CP concentration of the diet of stressed calves may need to be increased when feed intakes are low.

Serum copper, zinc, calcium and phosphorus concentrations of calves stressed by bovine respiratory disease and infectious bovine rhinotracheitis.

The relationship between serum minerals and stress and(or) disease has not been fully evaluated in beef cattle. Two trials were conducted to determine the changes in serum Cu and Zn during market-transit stress and(or) disease. Two additional trials were conducted to determine the changes in serum Cu and Zn after inoculation with infectious bovine rhinotracheitis virus (IBRV), with one of the trials determining the changes in serum Ca and P. Trials 1 (n = 80) and 2 (n = 100) utilized calves that were handled through a normal market-transit system and transported 1,967 km to the feedlot. Trials 3 (n = 37) and 4 (n = 8) used calves that were sero-negative to IBRV and then challenged with 2.7 x 10(5) plaque-forming units of the virus. Serum samples were collected at specified intervals and serum minerals were measured for each trial. Serum Zn for morbid or IBRV-challenged calves was decreased by 34, 57, 29 and 15% (P less than .05) for the four trials, respectively, at peak morbidity. Serum Cu of morbid or IBRV-challenged calves increased 5, 15, 40 and 33% for the four trials, respectively, at peak morbidity. Feed intakes were lower during morbidity for market-transit trials and after IBRV inoculation. Lower feed intake could partially explain the decrease in serum Zn; however, when feed intake was held constant, serum Zn concentration still decreased. Serum Zn decreased and serum Cu increased during market-transit morbidity or after IBRV.

Nutrient requirements of diseased, stressed cattle.

Cattle encounter numerous stressors during movement to feedlot or pastures for growing and finishing. Of utmost importance are diets that will be consumed and furnish the essential nutrients. Different diets and management systems may be required for different groups of cattle, and in this article, some nutrient requirements for these different groups are discussed.

Nitrogen kinetics of infectious bovine rhinotracheitis-stressed calves.

Eight crossbred feeder steers were used in two consecutive N balance studies to investigate the effects of infectious bovine rhinotracheitis virus (IBRV) on N kinetics. Balance Study 1, which followed a 10-d acclimation phase, consisted of 7 d of sample collection referred to as the healthy phase (d -7 to d -1). Study 2, the IBRV-infected phase, began 2 d after a nasal IBRV challenge and continued for 6 d (d 2 to d 8). A stable isotope, [15N]-glycine, was used to determine N kinetics in both studies. Steers weighed 203 kg at the beginning of the study, 208 kg at IBRV infection and 194 kg at the end of study. Infection with IBRV increased (P less than .05) urinary N excretion from 17.9 to 31.5 g/d. Daily N balance was reduced (P less than .05) during infection from 21.2 to -3.3 g/d. Total serum proteins increased (P less than .05) during infection from 6.6 to 7.1 g/100 ml, the increase being predominantly in the alpha and gamma globulin fractions. Blood urea-N increased (P less than .05) during infection from 6.5 to 12.9 mg/100 ml. The urine excretion curve of the stable isotope and the N balance data indicated that IBRV infection increased N turnover and altered tissue utilization of N.

Influence of protein concentration in prefast and postfast diets on feed intake of steers and nitrogen and phosphorus metabolism of lambs.

Two trials were conducted to determine the influence of prefast and postfast dietary protein concentration on feed intake of steers (avg wt 250 kg) and the N and P metabolism of lambs (avg wt 50 kg). In Trial 1, crossbred steers were fed prefast diets containing 8, 12 or 16% crude protein (CP) for 14 d before being deprived of feed and water for 24 h. Next, they received feed for 24 h and again were deprived for 48 h. Finally, they were fed diets containing either 10 or 15% CP. Steers fed the 16% CP prefast diet that were switched to the 10% CP realimentation diet tended to have lower feed intakes than the other fasted groups. In Trial 2, 16 crossbred lambs housed in metabolism stalls were fed prefast and postfast diets containing either 11 or 16% CP both before and after a 72-h fast in a 2 x 2 factorial arrangement. Nitrogen and P balance during realimentation tended to be affected by both the prefast and postfast dietary protein concentration. Results of this study indicate that CP content of the postfast diet alters repletion of nutrients lost during a feed and water deprivation period and can affect realimentation feed intake. However, the magnitude of this effect was dependent on protein content of the prefast diet.

Effect of transport on feeder calves.

One hundred fifty feeder steers (mean body weight, 195 kg) were assigned to 1 of 3 transport groups and were deprived of feed and water (fasted) for 24 hours. Additionally, calves were transported on a commercial livestock trailer for 0 (control-fasted only), 12 (short haul), or 24 (long haul) hours. Blood samples were obtained from the jugular vein before calves were loaded on the transport vehicle and immediately after calves of the long-haul group returned to the research feedlot. Complete blood counts were performed and 32 mineral, enzyme, and biochemical constituents were measured. Calf morbidity, mortality, and average daily weight gain were evaluated during the next 56 days. Duration of transport did not affect average daily gain; however, calves of the short-haul group had significantly (P less than 0.05) higher morbidity and mortality than did those of the control and long-haul groups. In all groups, results of differential leukocyte counts were indicative of stress response. Significant (P less than 0.05) linear contrasts were observed between duration of transport and erythrocyte, leukocyte, segmented neutrophil, lymphocyte, and eosinophil counts and results of serum enzyme (alanine transaminase, hydroxybutyrate dehydrogenase, total lactate dehydrogenase [LD], and LD-1, LD-3, and LD-4 isoenzymes), iron, urea nitrogen, beta-globulin, glucose, and urea nitrogen-to-creatinine ratio determinations. Significant (P less than 0.05) quadratic contrasts were observed between duration of transport and serum unsaturated iron binding capacity, total iron binding capacity, and LD-5 percentage. Calf source had a significant (P less than 0.05) effect on almost all variables tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of pre-fast dietary roughage content on recovery from feed and water deprivation in beef steers.

Sixty steer calves of mixed British breeding averaging 268 kg were randomly assigned to four treatment groups of 15 calves each to determine the influence of pre-fast dietary roughage content on recovery from feed and water deprivation. Three groups were fed diets containing either 84 (HR), 60 (MR) or 35% (LR) roughage at 1.75% of body weight for 3 d. Calves in these three groups were deprived of feed and water for 24 h, limit-refed and watered for 24 h, and deprived of feed and water for 48 h (deprivation). Calves were then fed the MR diet ad libitum for 2 wk. The fourth group of control steers was continuously fed the MR diet throughout the experiment. Realimentation weight gains and feed intakes were not affected by pre-fast diet roughage content. Blood packed cell volume increased (P less than .05) during deprivation. Blood potassium was not affected by deprivation but declined (P less than .05) upon refeeding. Plasma urea-N increased (P less than .05) during deprivation but returned to pre-fast concentrations by d 3 of realimentation. Ruminal volume was not significantly affected by deprivation but increased (P less than .05) by 50 to 100% upon refeeding. Ruminal fluid total volatile fatty acid (VFA) concentrations declined (P less than .05) during deprivation. On d 3 of realimentation, a linear contrast (P less than .05) was observed between total VFA concentrations and the pre-fast diet roughage content.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of pre-fast diet and transport on nitrogen metabolism of calves.

Two trials were conducted to determine the effects of transport stress and pre-transport diet on N losses, blood chemistry and ruminal variables of steers. In each trial, 16 crossbred steers (261 kg avg weight) were assigned to four groups in a 2 X 2 factorial arrangement of treatments. Treatments consisted of either transported or non-transported groups and two pre-transport dietary regimens (alfalfa hay or a 50% concentrate diet fed for 3 d before fasting). The alfalfa hay contained 14.6% crude protein (CP) and had a calculated metabolizable energy (ME) content of 1.92 mcal/kg. The 50% concentrate diet contained 15.5% CP and had a calculated ME content of 2.23 mcal/kg. Steers in the transport group were transported for 13 h in trial 1 and 46 h in trial 2, while the remaining steers were not transported. Both groups were withheld from feed and water during the observation periods. Urine and feces were collected and blood samples were obtained at intervals during the observation periods. Transport increased (P less than .05) urinary and total N excretion and nonevaporative water losses compared with fasting alone. Calves fed the 50% concentrate diet had lower N and nonevaporative water losses than calves fed hay, probably due to lower pre-fast N and water intakes. Ruminal total volatile fatty acid (VFA) concentrations and molar proportions of propionate and butyrate declined (P less than .05) with time in all groups, while molar proportions of acetate and minor VFA increased. Results of these trials indicate transportation stress can cause a significant increase in total N excretion and nonevaporative water loss compared with feed and water deprivation alone. Losses of N and water were lower in calves fed a 50% concentrate diet rather than hay for 3 d before the fasting period, probably because of lower pre-fast N and water intakes.

Nitrogen metabolism of calves inoculated with bovine adenovirus-3 or with infectious bovine rhinotracheitis virus.

Beef calves were inoculated with bovine adenovirus-3 or infectious bovine rhinotracheitis virus. After inoculation, plasma fibrinogen increased, serum phosphorus decreased, and nitrogen and phosphorus digestibility decreased compared with preinoculation values. Urinary N excretion increased when calves developed rectal temperatures greater than 39.7 C. Results indicated that clinical infection of calves with infectious bovine rhinotracheitis virus increases urinary N excretion and reduces N and phosphorus balance, and that clinical and subclinical infections with either virus reduce dietary N digestibility.