Comparison of single vaccination versus revaccination with a modified-live virus vaccine containing bovine herpesvirus-1, bovine viral diarrhea

virus (types 1a and 2a), parainfluenza type 3 virus, and bovine respiratory syncytial virus in the prevention of bovine respiratory disease in cattle
Douglas L. Step, dvm, dacvim; Clinton R. Krehbiel, phd; Luis O. Burciaga-Robles, mvz, mc; Ben P. Holland, ms; Robert W. Fulton, dvm, phd, dacvm; Anthony W. Confer, dvm, phd, dacvp; David T. Bechtol, dvm; David L. Brister, dvm; John P. Hutcheson, phd; Harold L. Newcomb, dvm
ObjectiveTo compare effects of administration of a modified-live respiratory virus vaccine once with administration of the same vaccine twice on the health and performance of cattle. DesignRandomized, controlled trial. Animals612 mixed-breed male cattle with unknown health histories. ProceduresCattle were randomly assigned to 1 of 2 treatment groups (single vaccination treatment group [SVAC group] vs revaccination treatment group [REVAC group]) during the preconditioning phase of production. All cattle were given a modified-live respiratory virus vaccine. Eleven days later, REVAC group cattle received a second injection of the same vaccine. During the finishing phase of production, cattle from each treatment group were either vaccinated a third time with the modified-live respiratory virus vaccine or given no vaccine. Health observations were performed daily. Blood and performance variables were measured throughout the experiment. ResultsDuring preconditioning, no significant differences were observed in performance or antibody production between groups. Morbidity rate from bovine respiratory disease was lower for SVAC group cattle; however, days to first treatment for bovine respiratory disease were not different between groups. No significant differences in body weights, daily gains, or dry-matter intake between groups were observed during the finishing phase. Revaccination treatment group cattle had improved feed efficiency regardless of vaccination protocol in the finishing phase. Conclusions and Clinical RelevanceVaccination once with a modified-live respiratory virus vaccine was as efficacious as vaccination twice in the prevention of bovine respiratory disease of high-risk cattle, although feed efficiency was improved in REVAC group cattle during the finishing period. (J Am Vet Med Assoc 2009;235:580587)

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eterinarians and producers readily recognize the potential negative impact that BRD has on health, treatment costs, performance, and carcass quality of cattle.1 Interaction between primary respiratory viruses (BHV1 also known as infectious bovine rhinotracheitis virus, PI3V, BVDV, and BRSV), bacteria (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni), and stress has been associated with serious clinical disease and loss. Weaned, young beef cattle are exposed to substantial stressors with changes in environment and nutrition, unfamiliar social interactions involved

Abbreviations
BHV1 BRD BRSV BVDV BVDV1a BVDV2a PI3V REVAC group SVAC group Bovine herpesvirus-1 Bovine respiratory disease Bovine respiratory syncytial virus Bovine viral diarrhea virus Bovine viral diarrhea virus type 1a Bovine viral diarrhea virus type 2a Parainfluenza type 3 virus Revaccination treatment group Single vaccination treatment group

From the Departments of Veterinary Clinical Sciences (Step) and Veterinary Pathobiology (Fulton, Confer), Center for Veterinary Health Sciences, and the Department of Animal Sciences, Division of Agricultural Sciences and Natural Resources (Krehbiel, Burciaga-Robles, Holland), Oklahoma State University, Stillwater, OK 74078; Palo Duro Consultation, Research, and Feedlot, 16851 Hope Rd, Canyon, TX 79105 (Bechtol); Intervet Inc, 1900 Wood Rd, Tolar, TX 76476 (Brister); Intervet Inc, 7101 Red Rock Rd, Amarillo, TX 79118 (Hutcheson); and Intervet Inc, 200 Watt St, Batesville, MS 38606 (Newcomb). Approved for publication by the Director of the Oklahoma Agricultural Experiment Station. Supported by project H-2438 and a grant from Intervet Incorporated. The authors thank Roy L. Ball for technical assistance. Address correspondence to Dr. Step. 580 Scientific Reports JAVMA, Vol 235, No. 5, September 1, 2009

with commingling, and transport to new production facilities. Because exposure to respiratory tract pathogens likely occurs through regular marketing channels, owners and veterinarians manage disease in high-risk cattle by implementing protocols that increase resistance to common respiratory tract pathogens. Increasing the degree of immunity in a group of cattle prior to the anticipated exposure to respiratory tract pathogens will usually decrease the severity and number of clinically affected individuals.2 Altering the degree of immunity in cattle can be accomplished by exposing them through vaccination to the various respiratory tract pathogens with timely programs. Because depressed immune response may occur in stressed cattle, preconditioning or backgrounding programs can help to build immunity in cattle prior to anticipated exposure to these respiratory tract pathogens. Several programs have demonstrated the health benefits of preconditioning.35 A substantial portion of the feeder calf supply exists in small herds throughout the United States, especially in the Southeast. It remains a necessity and common practice for recently weaned beef cattle to be assembled through various market outlets. These cattle are typically acquired in small numbers and then commingled with others of like size, weight, type, and sex and shipped to receiving facilities located in the High Plains. The stress associated with this production and marketing system and the time that often transpires to reach the preconditioning-backgrounding facilities result in a substantial number of such cattle being at high risk of exposure and development of BRD. Many recently weaned, young cattle arrive at these production units with minimal or no immunity to common viral respiratory tract pathogens. The challenge to the veterinarian and producer is to establish a heightened degree of immunity in these cattle as soon as possible after arrival while minimizing stress. Veterinarians frequently recommend administration of a modified-live respiratory virus vaccine for these high-risk cattle. Currently, there are no practical means to determine or measure which individuals either have been vaccinated or have responded to a dose of vaccine. Therefore, because of the stress that the newly received cattle undergo, many processing protocols for high-risk stressed cattle incorporate the administration of a modified-live BHV1-PI3VBVDV-BRSV vaccine shortly after arrival with subsequent vaccination in 1 to 2 weeks. Administration of the second dose of the modified-live virus vaccine is believed to stimulate the immune system in the group of stressed individuals that failed to respond to the first dose of vaccine. Thus, by incorporating 2 doses of the modified-live virus vaccine to the group or population, more cattle will develop protection or immunity when exposed under normal challenge situations. Careful inspection of labels of most modified-live virus vaccines indicates that administration of a single dose should confer immunity in clinically normal cattle. However, as mentioned, stressed cattle may not respond with an optimal immune response following a single dose of vaccine. Little data exist evaluating health, performance, and carcass merit of high-risk cattle vaccinated once versus twice against the comJAVMA, Vol 235, No. 5, September 1, 2009

mon viral respiratory tract pathogens. The purposes of the study reported here were to compare effects of administration of a modified-live BHV1-PI3V-BVDV1aBVDV2a-BRSV vaccine once with administration of the same vaccine twice on the health and performance of cattle and to compare effects of exposure to cattle persistently infected with BVDV on cattle that underwent vaccination once versus cattle that underwent vaccination twice. Materials and Methods AnimalsEight truckloads totaling 612 cattle (initial body weight, 219.5 23.6 kg [483 52 lb]; 221 bulls and 391 steers) were purchased from different cattle auctions in Arkansas and Oklahoma from January 16 through February 1, 2006, and delivered to the Oklahoma State University Willard Sparks Beef Research Center, Stillwater, Okla. The Oklahoma State University Institutional Animal Care and Use Committee approved this study. Procedures during preconditioning phase of productionUpon arrival, general health status of cattle was assessed and cattle were allowed to rest for approximately an hour in a dirt-surfaced pen. After the resting period, health was reassessed, each animal was individually weighed, male sex was confirmed, the presence or absence of testicles was determined, and each animal was identified with a unique numbered identification bangle ear tag. In addition, a small sample of skin was obtained from the ear (notch), fixed in buffered formalin, and submitted to the Oklahoma Animal Disease and Diagnostic Laboratory for immunohistochemistry testing to identify cattle persistently infected with BVDV. For each arrival date, cattle were stratified by reproductive status (bulls vs steers) and by body weight and assigned randomly within strata to 1 of 2 treatment groups (ie, SVAC group cattle and REVAC group cattle) in a randomized complete block design (2 weight blocks/arrival date/treatment). Treatment groups were randomly assigned to 1 of 24 pens (n = 12 pens/treatment [6 pens/treatment/weight block]; 22 to 29 cattle/pen). Because reproductive status of cattle at arrival varied by arrival date, the ratio of steers to bulls (newly castrated steers after processing) within pen varied by arrival date, but the number of steers and bulls was similar for each treatment. Following these procedures (ie, preprocessing), cattle were placed into holding pens and offered ad libitum access to prairie hay and water. Approximately 16 to 48 hours following arrival, cattle were individually weighed, given a 7-way clostridial bacterin-toxoid,a dewormed with fenbendazole oral suspensionb and an ivermectin topical pour-on,c implanted with 36 mg of zeranol,d and received 1 of 2 experimental treatments: a single needle-free vaccinatione with a modified-live virus vaccinef containing BHV1, PI3V, BVDV1a, BVDV2a, and BRSVf in the right neck area at processing (SVAC group cattle); or needle-free vaccinatione with a modified-live virus vaccinef containing BHV1, PI3V, BVDV1a, BVDV2a, and BRSV in the right neck area at processing followed in 11 days with needle-free revaccinatione by use of the same modified-live virus vaccinef in the left neck area (REVAC group cattle). The SVAC group
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cattle remained in their assigned pens on day 11 while the REVAC group cattle were handled through the processing chute. At initial processing, any sexually intact males were surgically castrated. In addition, 5 cattle/pen were randomly selected for collection of fecal samples. On day 11, fecal samples from the same 5 cattle/pen of the REVAC group were obtained. Immediately after collection, fecal samples were shipped to a commercial laboratory for determination of total fecal egg counts.g During processing, all products were administered following Beef Quality Assurance guidelines. For cattle from arrival date 2 (n = 204; 8 pens; 4 pens/treatment), a blood sample was collected from each animal via jugular venipuncture upon arrival. Samples were allowed to clot for 24 hours and centrifuged at 3,000 X g for 20 minutes at 4C, and serum was harvested and stored at 20C. Following processing and before cattle were moved to their home pen, cattle were weighed by pen on a platform scale and pen weight was recorded. Platform scale weight served as the starting weight for each pen. Cattle were then moved to their assigned dirt-floor, open-air pens (12.2 X 30.5 m [40 X 100 feet]). Steers were fed a 60% concentrate mixed ration formulated to meet or exceed nutrient requirements.6 Feed was mixed and delivered twice daily at 7:00 am and 1:00 pm by use of a rotary mixer wagon.h Prairie hay was supplied for the first 4 days of the receiving period and was decreased as intake of the mixed diet increased. Initially, the mixed diet was offered to the cattle at 1.5% of body weight and increased by 0.45 kg (1.0 lb)/steer daily until ad libitum consumption was achieved. Feed bunks were evaluated at approximately 6:00 am for any remaining feed not consumed the previous day, and daily feed delivery was adjusted before the 7:00 am feeding. Increases of 0.22 kg (0.50 lb)/steer/d were made when all the previous days feed had been consumed. Water was provided ad libitum via automatic water troughs that were positioned to supply water to 2 adjacent pens. All cattle were monitored daily for any abnormal clinical signs throughout the study by 1 of 3 evaluators. All 3 evaluators (DLS, LOB, and an assistant [Roy Ball]) responsible for evaluating the health of cattle were blinded as to the treatments assigned to each pen of cattle during the study to eliminate the introduction of potential bias. Because the most common clinical signs associated with high-risk cattle are those of BRD, evaluators used criteria based on an established systemi with some modifications to subjectively characterize or score any morbid cattle. Subjective criteria used to evaluate cattle for clinical signs of BRD were depression, appetite, and respiratory signs. The fourth criterion was an objective evaluation of rectal temperature. Signs of depression included depressed attitude, hanging head, glazed or sunken eyes, slow movement, arched back, difficulty getting up from lying down, knuckling or dragging toes when walking, and stumbling when moving. Signs relating to abnormal appetite included complete feed refusal, eating less than expected, slow eating (when considered different from an animals normal behavior), gaunt appearance, and obvious weight loss. Abnormal respiratory signs included obvious labored breathing, extended head and neck, and an audible noise during respirations.
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A severity score of 1 to 4 was recorded for each criterion, where 1 was mild, 2 was moderate, 3 was severe, and 4 was moribund. All cattle assigned a severity score were moved to the processing chute for rectal temperature evaluation. The fourth criterion, rectal temperature, was an objective evaluation used to determine whether antimicrobial treatment was to be administered. Any animal subjectively identified as morbid with a score of 1 or 2 and a rectal temperature of 40C (104F) or higher received an antimicrobial agent. All medications were administered according to the manufacturers label directions. In situations where the evaluators assigned a severity score of 3 or 4 to an animal, antimicrobial treatment was administered regardless of its rectal temperature. If an animal had a severity score of 1 or 2 but did not meet the rectal temperature criteria, no antimicrobial treatment was administered. After rectal temperature evaluation and, if necessary, antimicrobial administration was performed, all steers were returned to their respective home pens. Information was also recorded for any steer that required examination for any medical condition, such as digestive disorders, lameness, neurologic diseases, and abnormal swellings. Clinically affected cattle requiring treatment for BRD followed the standard treatment protocol for the beef research center. The first antimicrobial agent administered to steers was tilmicosinj at 10 mg/kg (4.5 mg/lb), SC, in the neck. If cattle required a second treatment at 48 hours after receiving their first treatment, enrofloxacink was administered at 10 mg/kg, SC, in the neck. If a third antimicrobial agent was required at 48 hours after the second treatment, ceftiofur HCll was given at 2.2 mg/kg (1 mg/lb), SC, in the neck. The same dose of ceftiofur HCll was repeated in 48 hours. If the steer was subjectively evaluated as still having clinical signs of BRD at 48 or 72 hours following the second dose of ceftiofur HCl,l a third dose was administered. Any animal that died or required euthanasia was submitted for a complete postmortem examination at the Oklahoma Animal Disease and Diagnostic Laboratory. Cattle that required euthanasia were administered xylazine,m IV , in the jugular vein for sedation followed by an overdose of pentobarbital,n IV , also administered in the jugular vein. Rectal temperatures, body weights, severity scores, and treatments were recorded for every animal that was examined for clinical signs of respiratory tract disease. Similarly, if an animal was examined for a medical condition other than respiratory tract disease, such as lameness, bloat, or neurologic abnormality, all information was recorded. Following a 60-day preconditioning-backgrounding period, cattle were weighed by pen and then individually to determine final weight. On day 59, steers received morning feed only and the water was turned off at approximately 6:30 pm before weighing the following morning beginning at approximately 7:00 am, in accordance with industry standards. For cattle from arrival date 2, a second blood sample was collected on day 60 and processed as already described. Serum samples were analyzed for antibody titerso against BHV1, PI3V , BRSV , BVDV1a, and BVDV2a. Procedures during finishing phase of productionAfter completion of the preconditioning phase, cattle in 8 pens (4 pens/treatment) were shipped to a research feedlotp for the finishing phase. At arrival, cattle were individually weighed,
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given a clostridial bacterin-toxoid,a dewormed with fenbendazole oral suspensionb and an ivermectin topical pour-on,c and implanted with 36 mg of zeranold; and cattle from each preconditioning treatment were assigned to receive one of the following treatments: vaccination with the modified-live respiratory virus vaccine containing BHV1, PI3V , BVDV1a, BVDV2a, and BRSVf or no vaccination with the modifiedlive respiratory virus vaccine. Cattle were assigned such that half of the cattle that had been vaccinated with a single dose of modified-live respiratory virus vaccine (ie, SVAC group cattle) and half of the cattle that had been vaccinated and revaccinated with the same vaccine (ie, REVAC group cattle) were assigned to each treatment during the finishing period. This approach resulted in a 2 X 2 factorial arrangement of treatments during the finishing phase. Therefore, the 4 treatment possibilities for cattle during the finishing phase were as follows: SVAC group cattle not vaccinated on arrival at the feedlot; SVAC group cattle vaccinated with the modified-live respiratory virus vaccinef on arrival at the feedlot, REVAC group cattle not vaccinated on arrival at the feedlot, and REVAC group cattle vaccinated with the modified-live respiratory virus vaccinef on arrival at the feedlot. Cattle from each treatment group were housed separately in dirt-floor pens equipped with an electronic monitoring systemq for individual dry-matter intake measurements. In addition, 2 cattle persistently infected with BVDV (noncytopathic type 1b) were introduced into each pen and remained in the pens throughout the finishing phase. Cattle were fed a diet formulated to meet or exceed nutrient requirements.6 Cattle were slaughtered at a commercial abattoirr following 157 days on feed at the conclusion of the experiment. Carcass data were collected by a commercial carcass data collection firm.s On the day of slaughter, hot carcass weight and incidence of liver abscesses were recorded. Longissimus muscle area, 12th rib back fat, marbling score (based on USDA graders determination), and USDA quality and yield grades were recorded after a 36-hour chill. Statistical analysisFor the preconditioning phase, data were analyzed as a randomized complete block design by use of a commercially available software program.t The fixed variable was treatment, whereas weight block within load was included in the model as a random variable. Pen served as the experimental unit for overall and BRD-related morbidity rate, overall and BRD-related mortality rate, mortality rate among BRD-affected cattle, treatment success rate for BRD, BRD-related relapse rate, rate of chronic BRD, weight gain, average daily gain, dry-matter feed intake, and dry-matter feed-to-gain ratio. Average weight gain, average daily gain, feed intake, and feed-to-gain ratios were calculated with and without data from cattle that died during the experimental period. For fecal and serum samples obtained at arrival and serum samples obtained on day 60, total fecal parasite egg counts and serum antibody titer data were analyzed.t Individual animal was used as the experimental unit. The fixed variable was treatment, whereas weight block within load was included in the model as a random variable. For the finishing phase, each animal served as the experimental unit for all performance and carcass merit response variables, and data were analyzed as a completely randomized design with a 2 X 2 factorial arrangement of treatments.t Carcass quality and yield grade data were analyzed.t Values of P 0.05 were considered significant.
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Table 1Mean serum antibody titers against common respiratory viral antigens in SVAC group cattle and REVAC group cattle on day 0 (SVAC group, n = 96; REVAC group, 100) and day 60 (SVAC group, 96; REVAC group, 100) at the preconditioning-backgrounding facility.

Variable

Treatment SVAC group REVAC group cattle cattle

SEM P F* 0.30 0.79 0.92 0.30 0.02 0.60 0.62 0.20

Day 0 BHV1 0.33 0.16 0.11 BRSV 7.97 8.56 2.04 BVDV1a 10.0 9.40 4.81 BVDV2a 7.37 3.24 2.83 Day 60 BHV1 5.04 2.16 0.91 BRSV 26.9 24.6 3.03 BVDV1a 161 179 25.9 BVDV2a 80.3 121 23.0 *Probability of an effect of revaccination.

Table 2Mean values of health variables of SVAC group cattle and REVAC group cattle at the preconditioning-backgrounding facility.

Variable No. of pens No. of steers No. of bulls

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Treatment SVAC REVAC group group cattle cattle 12 193 109 12 198 112

SEM P F* 0.99 0.99 0.35 0.56 0.65 0.20 0.26 0.35 0.84 0.29 0.17 0.11 0.05 0.04 0.55 0.46 0.67 0.67 0.72 0.34 0.21 0.48 0.64 0.17

Performance Initial body weight (kg) 213 212 7.80 Final body weight (kg) 303 301 10.7 Average daily gain (kg) 1.49 1.53 0.09 Dry-matter intake (kg/d) 8.35 8.08 0.27 Feed-to-gain ratio (kg/kg) 5.75 5.36 0.27 Performance Initial body weight (kg) 213 212 7.80 Final body weight (kg) 312 313 8.35 Average daily gain (kg) 1.65 1.68 0.04 Dry-matter intake (kg/d) 8.62 8.17 0.29 Feed-to-gain ratio (kg/kg) 5.22 4.87 0.16 Animal health Total morbidity rate (%) 37.0 44.7 5.58 BRD-related morbidity rate (%) 36.3 44.5 5.63 Other morbidity rate (%) 0.6 0.3 0.36 No. of days on feed 7.62 7.21 0.59 Treated 2 times (%) 29.0 25.6 5.42 Treatment success (%)# 71.0 74.4 5.42 Treated 3 times (%)** 5.29 4.51 1.91 Rate of chronic BRD (%) 13.6 8.7 3.93 Total mortality rate (%) 2.36 1.08 0.67 BRD-related mortality rate (%) 1.67 1.08 0.58 BRD-affected mortality rate (%) 3.33 2.43 1.45 Other mortality rate (%) 0.68 0.00 0.33

At the time of arrival. Calculated with data included from cattle that died or were removed from the study because of a medical condition. Calculated with data excluded from cattle that died or were removed from the study because of a medical condition. Mean days on feed at first treatment for signs of BRD. (Number of cattle treated 2 times for BRD/number of cattle treated 1 time for BRD) X 100. #Percentage of cattle treated once that were not treated again. **(Number of cattle treated 3 times for BRD/total number of cattle in pen) X 100. (Number of cattle treated 3 times for BRD/number of cattle treated 1 time for BRD) X 100. (Number of cattle that died as a result of BRD/number of cattle treated 1 time for BRD) X 100. = Not calculated. To convert kilograms to pounds, multiply value by 2.2. See Table 1 for remainder of key.

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Results Preconditioning phaseNo adverse reactions to the test treatments were apparent during processing, at the time of revaccination, nor at any other time during the study. Ten cattle died or were euthanatized during the entire study: 8 cattle resulting from causes related to the respiratory system and 2 cattle resulting from causes related to digestive disorders. Twelve cattle were removed from the experiment, 5 had problems related to the musculoskeletal system, 3 were identified to be persistently infected with BVDV on the basis of positive immunohistochemistry results, and 1 animal each had signs consistent with polioencephalomalacia, chronic bloat, behavioral problems identified as buller steer syndrome, or chronic pneumonia with failure to respond to treatments for BRD. The 3 cattle identified as persistently infected with BVDV were removed from the experiment 12 days after arrival. All 3 cattle persistently infected with BVDV were transported in loads that were not included in the finishing phase of this study. Two of the cattle persistently infected with BVDV had been assigned to the REVAC group, and 1 animal had been assigned to the SVAC group. Upon arrival, there was no significant (P = 0.52) difference in the number of total parasite eggs counted per kilogram of manure across treatment groups (5,086 vs 4,547 for SVAC group and REVAC group cattle, respectively). Parasite egg species that were identified were classified as stomach worms, Nematodirus sp, Cooperia sp, and tapeworm. Coccidia were also identified in cattle in the present study. The distribution of cattle that tested positive for each parasite was as follows: 87% tested positive for stomach worms (88.3% of SVAC group cattle vs 85.9% of REVAC group cattle; P = 0.89), 52.1% tested positive for Nematodirus sp (59% of SVAC group cattle vs 54.3% of REVAC group cattle; P =

0.50), 93.2% tested positive for Cooperia sp (95% of SVAC group cattle vs 91.2% of REVAC group cattle; P = 0.95), 17.1% tested positive for tapeworm (13.3% of SVAC group cattle vs 21.0% of REVAC group cattle; P = 0.86), and 59% tested positive for coccidia (93.3% of SVAC group cattle vs 89.2% of REVAC group cattle; P = 0.94). For REVAC group cattle, by day 11 after arrival, the number of total parasite eggs counted per kilogram of manure was undetectable. Mean serum antibody titers were determined (Table 1). There were no significant differences in antibody titers between SVAC group cattle and REVAC group cattle at the time of arrival. Evidence of response to the vaccinations was measured by increases in all antibody titers against BHV1, PI3V , BVDV1a, BVDV2a, and BRSV by day 60. On day 60, antibody production to BHV1 antigen was significantly (P = 0.02) greater for SVAC group cattle than for REVAC group cattle. No other differences in antibody titers (against PI3V , BVDV1a, BVDV2a, and BRSV) were observed. All cattle had serum neutralizing antibody titers against BVDV1a and BVDV2a at the end of the preconditioning phase of the study. Performance variables (Table 2) were not affected by treatment (SVAC group cattle vs REVAC group cattle) during the 60-day preconditioning period when calculated with and without data from cattle that died or were removed from the study because of medical conditions that occurred during the experimental period. Total morbidity rate was significantly (P = 0.05) lower (37% vs 44.7%) for SVAC group cattle, compared with REVAC group cattle. Similarly, BRD-related morbidity rate was significantly (P = 0.04) lower (36.3% vs 44.5%) for SVAC group cattle, compared with REVAC group cattle. However, no significant (P = 0.46) difference in days to first treatment for BRD was observed between treatment groups (7.62 vs 7.21 days for SVAC

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Table 3Effect of vaccination upon arrival at the feedlot on mean performance variables of SVAC group cattle and REVAC group cattle. Variable No. of cattle No. of days on feed Initial body weight (kg) Final body weight (kg) REVAC group cattle No vaccination Vaccination 40 157 325 565 39 157 323 569 SVAC group cattle No vaccination 40 157 329 574 Vaccination 40 157 329 562 SEM 4.13 7.30 Pre 0.19 0.86 P F* Fin 0.84 0.59 Pre X Fin 0.82 0.27 0.78 0.43 0.13 0.38 0.64 0.90 0.67 0.08 0.61 0.29 0.98 0.14

Performance Average daily gain (kg) 1.53 1.57 1.56 1.48 0.03 0.40 0.55 Dry-matter intake (kg) 10.9 11.0 11.2 11.0 0.18 0.49 0.66 Feed-to-gain ratio (kg/kg) 7.16 7.07 7.24 7.50 0.11 0.02 0.45 Carcass merit Hot carcass weight (kg) 363 368 369 365 5.03 0.76 0.99 Dressing (%) 64.3 64.6 64.4 64.9 0.33 0.53 0.22 12th rib fat (cm) 1.19 1.16 1.16 0.19 0.07 0.63 0.59 Kidney-pelvic-heart fat (%) 1.92 1.91 1.92 1.88 0.03 0.71 0.45 Marbling score 381 402 415 389 11.79 0.51 0.65 Quality grade Yield grade 2.49 2.56 2.54 2.46 0.15 0.87 0.98 Prime and choice (%) 31.6 37.5 43.6 33.3 7.90 0.61 0.78 Select (%) 55.3 62.5 53.8 64.1 8.10 0.86 0.34 Liver abscesses (%) 0.07 0.17 0.05 0.02 0.06 0.03 0.38

At the start of the finishing phase of production. Traces = 200, slight = 300, small = 400, modest = 500, moderate = 600, and slightly abundant = 700. Pre = Preconditioning phase of production. Fin = Finishing phase of production. See Tables 1 and 2 for remainder of key. 584 Scientific Reports JAVMA, Vol 235, No. 5, September 1, 2009

group cattle and REVAC group cattle, respectively). No other differences in health response variables were observed. Finishing phaseCattle were on feed for 157 days during the finishing period. No cattle had any abnormal signs consistent with BRD that would have required antimicrobial treatment during the finishing phase (data not shown). The preconditioning phase X finishing phase vaccination treatment interaction was not significant for any performance variables. In addition, there were no significant differences in initial or final body weights, average daily gain, or dry-matter intake as the result of preconditioning or finishing phase vaccination protocols (Table 3). However, REVAC group cattle had a significantly (P = 0.02) lower (improved) feed-to-gain ratio, compared with SVAC group cattle, during the finishing phase. Carcass meritPreconditioning or finishing vaccination protocols had no significant effects on hot carcass weight, dressing percent, longissimus muscle area, 12th rib fat thickness, kidney-pelvic-heart fat, or quality and yield grade (Table 3). Preconditioning treatment X finishing period interaction was not significant (P = 0.08) for marbling score. However, marbling score was greater for REVAC group cattle that were vaccinated during the finishing phase and for SVAC group cattle that were not vaccinated during the finishing phase, compared with cattle receiving the other vaccination protocols. There was a significantly (P = 0.03) greater incidence of liver abscesses observed in the REVAC group cattle, compared with SVAC group cattle, regardless of vaccination protocol at the beginning of the finishing phase. Discussion Preconditioning of weaned steers has been a tool available for producers and cattle buyers to improve health and decrease economic losses associated with BRD, the most common disease in feedlot cattle.3 Although several preconditioning programs have been developed by universities, producer organizations, and animal health-care companies, the common denominator of these programs is the inclusion of viral respiratory vaccines upon arrival at the preconditioning-backgrounding facility followed by revaccination 10 to 14 days later.7 Other common management procedures during preconditioning programs include castration of sexually intact males, dehorning, and treatment for internal and external parasites.8 The preconditioning program used in this study confirmed the benefit of reduced health problems in the finishing phase in which none of the cattle were observed to have clinical signs of BRD. Also, there appeared to be protections against BVDV afforded to the cattle. Protection against BVDV in this study may have been the result of exposure to cattle persistently infected with BVDV either in transit prior to day 0 of the study or in adjacent pens up to 11 days after processing. Alternatively, protection against BVDV may have been the result of vaccination with the modified-live virus vaccine that contained BVDV1a and BVDV2a.
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Results of other studies9,10 indicate that cattle with high parasite loads have decreased antibody production in response to vaccination, compared with cattle that had been dewormed. In the present study, fecal parasite counts of the random subpopulation of cattle in each pen confirmed that, upon arrival, all cattle that were tested had positive results to at least 1 common internal parasite. There was no significant difference in total parasite counts per kilogram of manure across treatments when cattle arrived at the preconditioning facility. Retesting of newly collected fecal samples from the same cattle on day 11 revealed that these cattle were negative for internal parasites. The timing of the second fecal sample on day 11 in this study was for convenience of collection, which occurred on the same day as revaccination to minimize any additional stress that would have occurred on the selected cattle. Although evaluating the efficacy of a deworming strategy was not an objective of the present study, benefits of including deworming strategies when implementing preconditioning health programs may include an increased opportunity for cattle to mount an immune response9 and increased daily gain and feed efficiency.11 During the preconditioning phase, there was no significant difference in performance between treatment groups. These results are in general disagreement with what has been expressed anecdotally in the industry; where concern exists for when cattle are moved from their home pen to the processing facility for revaccination or reimplanting, the stress that cattle are exposed to results in decreased dry-matter intake and average daily gain, compared with cattle that are left in their home pen. Handling and administering a placebo to the SVAC group cattle on day 11 would have eliminated potential confounding results between REVAC group cattle and SVAC group cattle in our study. We agreed that SVAC group cattle would not be moved from their home pen unless for medical reasons to reflect common industry practices. However, to our knowledge, studies are lacking regarding effects of cattle movement through the processing facility on short- or long-term animal performance. In the present study, moving REVAC group cattle from their home pens after 11 days on feed had no detrimental effect on 60-day performance values, compared with those of SVAC group cattle. Distance to the processing facility, time away from feed and water, and handling methods most likely contribute to differences observed in health and performance of cattle among feed yards. If cattle are frightened or more nervous in nature when moved about in a facility and are stressed, differences in performance may be observed. In the present study, although there was no significant difference in performance between groups in the preconditioning phase, there was an increased total morbidity rate for REVAC group cattle, compared with that of SVAC group cattle. Similarly, BRD-related morbidity rate was increased for REVAC group cattle, compared with that of SVAC group cattle, during the preconditioning phase. However, when the number of days on feed until first treatment for BRD was compared, there were no significant differences (7.62 vs 7.21 days) between SVAC group cattle and REVAC group cattle, respectively. Therefore, we concluded that
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the increased total and BRD-related morbidity rates for REVAC group cattle were most likely an artifact of the randomization process because morbidity events occurred before the administration of the second dose of vaccine (day 11). No significant differences in treatment success, rate of cattle with chronic BRD, or mortality rate were observed across treatment groups during the preconditioning phase. Another tool that has been used to determine the effectiveness of vaccines has been changes in antibody titers against antigens present in the vaccine, which is currently the only measurement required by the USDA to license a vaccine in the United States. In the present study, there were no significant differences in antibody titers against antigens present in the vaccine upon arrival. However, at the end of the preconditioning phase, the mean antibody titer against BHV1 in REVAC group cattle was lower, compared with that of SVAC group cattle. There were no significant differences in antibody titers against any other of the vaccinal antigens. These results were in disagreement with previous results that reported an increase in antibody production in cattle that received a second modified-live respiratory virus vaccine, compared with cattle that received only a single dose.12 Although the lower antibody titers against BHV1 could be considered a disadvantage for REVAC group cattle, others have reported that there is no direct relationship of antibody titers against a specific antigen and protection to that disease.1315 In addition, antibody production is not only stimulated by vaccination but also by exposure to disease.16,17 In the present study, the increased antibody titers against BHV1 in SVAC group cattle could be a reflection of a higher incidence of this virus in the population included in this treatment group and not by a better response to the vaccine. The collection and analysis of additional serum samples or nasal swabs for viral isolation and antibody titers at the time of antimicrobial administration could have been beneficial when investigating the response to viral and bacterial pathogens involved in BRD. During the 157 days of the finishing phase, there were no significant differences in animal performance except for an improvement in feed efficiency for cattle that were in the REVAC group, compared with cattle that were in the SVAC group. During the finishing phase, a steer persistently infected with BVDV was introduced into each pen to provide a model of disease challenge. When a steer persistently infected with BVDV was introduced into the pen or adjacent pens, a decrease in performance was measured in 1 study.18 Results of that study are interesting because the vaccination history of the cattle was unknown and the cattle were only processed upon arrival at the feedlot. In the present study, exposure to a steer persistently infected with BVDV during the finishing phase of production resulted in poorer feed efficiency of SVAC group cattle, compared with REVAC group cattle. Although there was no significant difference in antibody titers against BVDV1a or BVDV2a at the end of the preconditioning phase between treatment groups, there could be a possible negative effect on performance by exposure to BVDV, as previously reported, in cattle that received only 1 modified-live respiratory virus vaccine during
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the preconditioning phase, regardless of the administration of a modified-live respiratory virus vaccine upon arrival to the feedlot. A more detailed serologic and epidemiologic analysis would be required to confirm and investigate these results further. Results from a recent study19 suggest that exposing previously vaccinated, freshly weaned, transport-stressed beef cattle to an animal persistently infected with BVDV had no effects on performance or carcass characteristics, which are similar to the findings of the present study. No significant differences in carcass characteristics were observed in this study as a result of vaccination during preconditioning or upon arrival to the feedlot. Bovine viral diarrhea is generally considered a subclinical disease that is difficult to diagnose in the field unless it is complicated with other viral or bacterial diseases. Therefore, cattle that are infected with this BVDV may not have abnormal clinical signs and thus may not be examined. Finding no significant differences in carcass merit suggested that either preconditioning vaccination protocol (vaccinated vs revaccinated), regardless of the feedlot protocol (no vaccination or a single viral modified-live respiratory virus vaccine upon arrival), has no detrimental effects on carcass merit. The results of this study suggested that single vaccination was as efficacious as revaccination with a modified-live respiratory virus vaccine in high-risk cattle for immunization against common viral respiratory tract pathogens associated with BRD, although feed efficiency was improved in REVAC group cattle, compared with SVAC group cattle, during the finishing period. Because multiple risk factors are involved with morbidity rate in recently weaned beef cattle, we suggested a veterinarian be consulted for health recommendations on specific loads of cattle under specific receiving conditions before the decision is made to vaccinate only once with a modified-live respiratory virus vaccine. Our results also indicated that appropriate preconditioning strategies can have a dramatic positive impact on decreasing morbidity rate and the associated negative economic impacts from BRD when cattle are maintained as individual groups throughout the finishing phase, even when exposed to cattle persistently infected with BVDV.
a. b. c. d. e. f. g. 20/20 Vision 7 with Spur, Intervet Inc, Millsboro, Del. Safe-Guard Suspension 10%, Intervet Inc, Millsboro, Del. Ivomec Pour On, Merial, Duluth, Ga. Ralgro, Schering-Plough Animal Health, Kenilworth, NJ. Pulse Needle-Free Systems, Lenexa, Kan. Vista 5 SQ, Intervet Inc, Millsboro, Del. Fecal eggs per kilogram analysis was performed by Dr. Gene White, Animal Production Consulting, Lincoln, Neb. h. Roto-Mix, Dodge City, Kan. i. DART system, Pharmacia Upjohn Animal Health, Kalamazoo, Mich. j. Micotil 300, Elanco Animal Health, Indianapolis, Ind. k. Baytril 100, Bayer Corp, Shawnee Mission, Kan. l. Excenel RTU, Pfizer Inc Animal Health Group, New York, NY. m. X-JECTE, Butler Animal Health Supply, Dublin, Ohio. n. Beuthanasia-D Special (Euthanasia Solution), Schering-Plough Animal Health Corp, Union, NJ. o. Serum samples shipped to Dr. Richard Mock, Texas Veterinary Medical Diagnostic Laboratory, Amarillo, Tex. p. Palo Duro Consultation, Research, and Feedlot, Canyon, Tex. q. GrowSafe Systems, Airdrie, AB, Canada. r. Cargill Meat Solutions, Plainview, Tex. JAVMA, Vol 235, No. 5, September 1, 2009

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Carcass data collected by Dr. Ty Lawrence, West Texas A&M University, Canyon, Tex. Proc Mixed, SAS, version 8.02, SAS Institute Inc, Cary, NC.

11.

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