Deposition and clearance of radiolabelled monodisperse polystyrene spheres in the calf lung

Two groups of three calves were exposed to monodisperse aerosols of radiolabelled polystyrene spheres measuring 3.3 microns in aerodynamic diameter (SD 0.3 micron). Although the spheres preferentially deposited in the trachea and major bronchi, 72 per cent of the total radioactivity deposited was found in lung tissue beyond the major bronchi. Mean alveolar deposition, estimated from the end retention value after mucociliary clearance, was 34 per cent in the group of bull calves and 52 per cent in the group of heifer calves. Alveolar deposition increased from 47 to 56 per cent (P less than 0.05) in heifer calves treated with oestradiol. Mucociliary clearance of the spheres was unaffected by repeated exposure to the experimental aerosol and the overall mean mucociliary clearance rate constant was 1.28 (+/- 0.43) h-1 (half-life 32 minutes). Clearance curve profiles tended to be characteristic for individual calves but variation in mucociliary clearance rates within calves was high and on occasions clearance rate inexplicably fell to 10 to 50 per cent of the maximum achievable value for the calf. Neither mucociliary clearance rate nor alveolar deposition was affected by a change in climate from 14 degrees C, 87 per cent relative humidity to 5 degrees C, 75 per cent relative humidity. Both alveolar deposition and mucociliary clearance of the spheres could be manipulated using a beta-adrenergic treatment.     

Proliferation of Pasteurella haemolytica in the calf respiratory tract after an abrupt change in climate

Two groups of four calves were exposed to a poly-disperse aerosol of 1.3 X 10(4) to 16 X 10(4) colony forming units (CFU) of nalidixic acid resistant Pasteurella haemolytica type A1 litre-1 of air with a mass median aerodynamic diameter of 2.6 +/- 0.8 microns. One group of calves was kept at 5 degrees C, 72 per cent relative humidity (RH) and the second was subjected to an abrupt change in climate directly after aerosol exposure from 5 degrees C, 75 per cent RH to 13 degrees C, 84 per cent RH. Clearance of the organism from the respiratory tract of the calves was monitored over the subsequent 23 hours by a method of tracheal and nasopharyngeal swabbing. Clearance measured at the trachea in all calves in both groups was not a continuous, uninterrupted process but exhibited a temporary decline between eight and 14 hours. Calves subjected to an abrupt change in climate after aerosol challenge had raised respiratory rates eight to 14 hours later and P haemolytica proliferated in the nasopharynx over the entire 23 hours. There was no apparent effect of climate on P haemolytica in the trachea. It is suggested that rapid growth of P haemolytica accompanying a change in climate may be an important aetiological factor in pneumonic pasteurellosis of calves.     

Consequences of short term fluctuations of environmental temperatures in calves--Part 1: Immediate reactions of the respiratory system, the cardiovascular system, metabolism and thermal regulation

Clinically healthy calves (aged 3-6 weeks) were exposed to defined ambient temperature for 4 hours (cold: 5 degrees C, 60% humidity, n = 12; warm: 35 degrees C, 60% humidity, n = 11). During the exposure of each animal in a climatic chamber, certain parameters of lung function, respiratory mechanics, blood gas analysis, circulation, metabolism and thermal regulation were registered simultaneously in order to study immediate physiological consequences of different environmental conditions. In comparison to control calves (18-20 degrees C, 60% humidity, n = 13) an insufficient adaptation of these young calves was noticed in both cold and warm conditions. At 5 degrees C, marked changes in lung function were observed, i.e. airway constriction, pulmonary hypertension, and ventilation-perfusion-mismatching leading to hypoxemia and hypercapnia. Due to compensation by the circulatory system, a sufficient O2-consumption of the organism as well as an unchanged body temperature were maintained. At 35 degrees C, the respiratory pattern changed to panting and a higher dead space ventilation. No changes were observed in pulmonary gas exchange and blood arterialisation. Due to hyperventilation, the partial pressure for CO2 decreased in blood. Since the body temperature increased continuously, thermal regulation was insufficient. This situation would have led to animals collapsing after a period of heat stress lasting longer than 4 hours. In conclusion, young calves up to the age of 6 weeks were not able to tolerate acute changes in ambient temperature. This was true for cold conditions (5 degrees C) as well as for hot conditions (35 degrees C). The results of this study should be taken into account in order to optimise transport and farming conditions.     

Histological features of respiratory epithelium of calves held at differing temperature and humidity.

The effect of ambient temperature and humidity on the structure of respiratory epithelium of calves was studied. Four calves of each of three experiments were acclimatized to a nonoperational environmental chamber for six days and then exposed to constant extremes of temperatures and relative humidity of one of 30 degrees C --35%, or 27 degrees C--92%, or 5 degrees C--92% respectively in this chamber for eight days each. Five calves (3 and 2) were similarly acclimatized then exposed to 1 degrees C--40%. Nasal swabs were taken from all animals at regular intervals. Swabs of three animals yielded Mycoplasma spp. and one swab yielded the virus of infectious bovine rhinotracheitis. Detailed histological studies of respiratory epithelium of nose, trachea, major bronchus and terminal bronchioli were conducted at four sites. Goblet cells were least in calves held in hot and dry air; calves held in dry air had the least polymorphonuclear cells and the greatest prevalence of hypochromatic cell layers and vacuolation of epithelial cells. Differences between experiments were evident most for sites of trachea and major bronchus.     

OBSERVATIONS OF SW AINSONA GALEGIFOLIA POISONING IN CATTLE IN NORTHERN NEW SOUTH WALES

A mild interstitial pneumonia with mononuclear cell infiltration was produced in calves following intra-tracheal inoculation of the BIL adenovirus. Viral antigen appeared early in the regional lymph node. An interstitial reaction developed early in the lungs, and pneumonic lesions and infective virus were present by the third day after inoculation. Virus spread rapidly to trachea, tonsils and nasal mucosa, and was excreted from the third to eighth day. Upper and lower respiratory tissues continually harboured virus until the 12th day, when the experiment was terminated. The virus was isolated from the livers of two calves. All tissues yielded low concentrations of virus, and only the lung showed pathological reactions. The reactions were qualitatively similar to known adenovirus pneumonias, but considerably milder, and lacked the characteristic necrotic and proliferative bronchiolar changes.     

EXPERIMENTAL ADENOVIRUS PNEUMONIA IN CALVES

A mild interstitial pneumonia with mononuclear cell infiltration was produced in calves following intra-tracheal inoculation of the BIL adenovirus. Viral antigen appeared early in regional lymph node. An interstitial reaction developed early in the lungs, and pneumonic lesions and infective virus were present by the third day after inoculation. Virus spread rapidly trachea, tonsils and nasal mucosa, and was creted from the third to eighth day. Upper and lower respiratory tissues continually harboured virus until the 12th day, when the experiment was terminated. The virus was isolated from the livers of two calves. All tissues yielded low concentrations of virus, and only the lung showed pathological reactions. The reactions were qualitatively similar to known adenovirus pneumonias, but considerably milder, and lacked the characteristic necrotic and proliferative bronchiolar changes.     

Experimental production of bovine respiratory tract disease with bovine viral diarrhea virus

Five 6-month-old calves were inoculated with bovine viral diarrhea (BVD) virus (n = 3) or Pasteurella haemolytica (n = 2) endobronchially with a fiberoptic bronchoscope. Five additional calves were inoculated sequentially with BVD virus followed by P haemolytica at a 5-day interval. Blood samples were collected daily from the calves for bacterial isolation. Clinical signs of respiratory tract disease in calves were recorded daily. If the calves survived, they were killed for necropsy 3 or 4 days after inoculation with P haemolytica (or 8 days after inoculation with BVD virus). The extent and nature of pulmonary lesions in the calves were determined, and the lower portion of the respiratory tract (lungs and trachea) was examined for both these organisms. The 3 calves, inoculated with BVD virus only, developed mild clinical signs mainly manifested as fever, nasal discharge, and occasional cough. Approximately 2% to 7% of the total lung capacity of these calves was pneumonic. Mild clinical signs and localized lesions involving about 15% of the lung volume developed in the 2 calves exposed to P haemolytica only. However, severe fibrinopurulent bronchopneumonia and pleuritis involving 40% to 75% of lung volume developed in the 5 calves inoculated sequentially with BVD virus and P haemolytica. The possible role BVD virus may have in bovine respiratory tract disease is discussed.     

Scanning electron microscopic study of the lower respiratory tract in calves and adult cattle

The surface characteristics of the lower respiratory tract of two groups of cattle were studied with the scanning electron microscope. Group A comprised six one-week-old calves and group B four adult cows. None of the animals had overt respiratory disease or gross morphological evidence of pulmonary lesions. The trachea, bronchi, bronchioles and alveoli of the cranial and the caudal lobes of the right lung were examined. In both groups the luminal surface of the trachea and large bronchi were completely covered by cilia, apparently forming an efficient mucociliary escalator. In the adult animals there were some patchy areas in the trachea and large bronchi devoid of ciliated cells; these were considered abnormal. In the bronchi, non-ciliated cells, mainly mucus-secreting, were not easily identified unless they were discharging secretion. In small bronchi, non-ciliated cells were more evident and easily seen. The bronchioles had many non-ciliated cells and very few ciliated cells capable of forming a complete carpet for a mucociliary escalator. Types 1 and 2 alveolar epithelial cells and alveolar macrophages were identified in both groups. Pores of Kohn were found in the alveolar walls in all animals.     

Establishment of an attenuated strain of bovine respiratory syncytial virus for live virus vaccine

To develop a live virus vaccine for the prevention of bovine respiratory syncytial (BRS) virus infection in calves, an attempt was made to produce an attenuated virus. The RS-52 strain of BRS virus, isolated from the nasal secretions of a naturally infected calf, was subjected to serial passages in adult hamster lung established (HAL) cells at 30 degrees C and the attenuated rs-52 strain as a live virus vaccine was established. The rs-52 strain multiplied better at 30 degrees C than at 34 or 37 degrees C in HAL cells. The differences in the highest virus titers of this strain between the culture temperature of 30 degrees C and that of 34 or 37 degrees C were more than 2.25 log TCID50. Colostrum-deprived newborn calves and 2 approximately 4 months old calves inoculated with the rs-52 strain manifested no abnormal clinical sings at all. However, all inoculated calves produced serum neutralization antibody. When the colostrum-deprived newborn calves immunized with the rs-52 strain were challenged with the virulent NMK7 strain of BRS virus, they exhibited no pyrexia or other abnormal clinical signs at all. An attempt was made to recover the virus from nasal secretions of these calves, but in vain. On the other hand, a nonimmunized control colostrum-deprived newborn calf developed slight fever, mild cough, and slight serous nasal discharge after challenge exposure. The virus was recovered from nasal secretions of this calf. From these results, it was considered that the rs-52 strain could be used as an attenuated live virus vaccine for prevention of BRS virus infection.     

Lack of virus transmission from bovine viral diarrhoea virus infected calves to susceptible peers

None of 14 calves not previously exposed to BVDV became infected after being forced to have nose-to-nose contact with a group of 5 calves primarily infected with BVDV. These were 5 male calves primarily infected with a type I BVDV strain, after nose-to-nose contact with a persistently viraemic calf. All 5 became infected and were clinically affected. They were slightly depressed and pyretic at 8-9 days post-infection, with a body temperature of up to 41.6 degrees C, but no medical treatment was required. Seroconversions to BVDV were detected in these calves at 14 to 21 days post-infection. The 14 healthy calves, proved to be free from BVD virus--as well as antibodies, were introduced 2 by 2 into the group of 5 primarily infected calves on days 4, 7, 14, 21, 28, 35 and 42 after the 5 calves had been in contact with the persistently BVDV-infected calf. Each pair of calves stayed within the primarily infected group for 2 days. None of these 14 calves seroconverted to BVDV.     

Mast cells in the bovine lower respiratory tract: morphology, density and distribution

The lower respiratory tract of six 8-day-old calves and six adult cows was fixed in either isotonic formal-acetic-acid or neutral buffered formalin in order to study the morphology, density and distribution of mast cells. They were found at all levels of the tract with the highest density in the major bronchi. Tissues from cows had significantly more mast cells than those from calves. There were significantly more mast cells detected in calf airways fixed with isotonic formal-acetic-acid compared with those seen in the same tissues fixed with neutral buffered formalin. Regardless of the age and fixation, mast cells were located predominantly in the alveolar septa and in the lamina propria of airways. They were also commonly encountered within the mucosal epithelium of the trachea. Ultrastructurally, mast cells in bovine airways and lung contained two types of intracytoplasmic granules as described in other species.     

Transmission of Bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves

Bovine viral diarrhea virus (BVDV) persistently infected (PI) calves represent significant sources of infection to susceptible cattle. The objectives of this study were to determine if PI calves transmitted infection to vaccinated and unvaccinated calves, to determine if BVDV vaccine strains could be differentiated from the PI field strains by subtyping molecular techniques, and if there were different rates of recovery from peripheral blood leukocytes (PBL) versus serums for acutely infected calves. Calves PI with BVDV1b were placed in pens with nonvaccinated and vaccinated calves for 35 d. Peripheral blood leukocytes, serums, and nasal swabs were collected for viral isolation and serology. In addition, transmission of Bovine herpes virus 1 (BHV-1), Parainfluenza-3 virus (PI-3V), and Bovine respiratory syncytial virus (BRSV) was monitored during the 35 d observation period. Bovine viral diarrhea virus subtype 1b was transmitted to both vaccinated and nonvaccinated calves, including BVDV1b seronegative and seropositive calves, after exposure to PI calves. There was evidence of transmission by viral isolation from PBL, nasal swabs, or both, and seroconversions to BVDV1b. For the unvaccinated calves, 83.2% seroconverted to BVDV1b. The high level of transmission by PI calves is illustrated by seroconversion rates of nonvaccinated calves in individual pens: 70% to 100% seroconversion to the BVDV1b. Bovine viral diarrhea virus was isolated from 45 out of 202 calves in this study. These included BVDV1b in ranch and order buyer (OB) calves, plus BVDV strains identified as vaccinal strains that were in modified live virus (MLV) vaccines given to half the OB calves 3 d prior to the study. The BVDV1b isolates in exposed calves were detected between collection days 7 and 21 after exposure to PI calves. Bovine viral diarrhea virus was recovered more frequently from PBL than serum in acutely infected calves. Bovine viral diarrhea virus was also isolated from the lungs of 2 of 7 calves that were dying with pulmonary lesions. Two of the calves dying with pneumonic lesions in the study had been BVDV1b viremic prior to death. Bovine viral diarrhea virus 1b was isolated from both calves that received the killed or MLV vaccines. There were cytopathic (CP) strains isolated from MLV vaccinated calves during the same time frame as the BVDV1b isolations. These viruses were typed by polymerase chain reaction (PCR) and genetic sequencing, and most CP were confirmed as vaccinal origin. A BVDV2 NCP strain was found in only 1 OB calf, on multiple collections, and the calf seroconverted to BVDV2. This virus was not identical to the BVDV2 CP 296 vaccine strain. The use of subtyping is required to differentiate vaccinal strains from the field strains. This study detected 2 different vaccine strains, the BVDV1b in PI calves and infected contact calves, and a heterologous BVDV2 subtype brought in as an acutely infected calf. The MLV vaccination, with BVDV1a and BVDV2 components, administered 3 d prior to exposure to PI calves did not protect 100% against BVDV1b viremias or nasal shedding. There were other agents associated with the bovine respiratory disease signs and lesions in this study including Mannheimia haemolytica, Mycoplasma spp., PI-3V, BRSV, and BHV-1.     

Single-dose treatment of neonatal calf pneumonia with the new macrolide antibiotic tilmicosin

Tilmicosin, a new macrolide antibiotic, 20-deoxo-20-(3,5-dimethylpiperidin-l-yl)desmycosin, formerly identified as EL-870, has been evaluated in three experiments as a single subcutaneous injection at dosages of 10, 20 or 30 mg/kg for the treatment of naturally occurring pneumonia in neonatal calves. Male Holstein calves, under five days of age, were shipped from Wisconsin and housed in pens. They were assigned sequentially to a treatment group when their temperature was greater than or equal to 39.7 degrees C for two consecutive days or greater than or equal to 39.7 degrees C and signs of respiratory disease were present. Clinical signs were evaluated daily for 14 days after the tilmicosin treatment. Calves that died and those that survived for the 14 day experimental period were examined post mortem. Treatment with tilmicosin was effective at all dosage levels, as determined by significant (P less than or equal to 0.05) reductions in body temperature within 24 hours, in the number of animals that died, in the incidence and severity of clinical signs, in the number of Pasteurella species found in lung tissue and in the severity of the pneumonic lesions. In two of the three experiments severe outbreaks of cryptosporidiosis resulted in significant mortalities within a few days after the arrival of the calves. Treatment with tilmicosin was effective against respiratory disease even in the presence of this severe concurrent disease.     

Studies on the pathogenesis and interspecies transmission of respiratory syncytial virus isolated from sheep

Inoculation of lambs with an ovine isolate of respiratory syncytial virus (RSV) by a combined intranasal and intratracheal route resulted in mild respiratory tract illness, with respiratory tract lesions. Lung lesions were characterized by bronchitis and bronchiolitis, hyperplasia of bronchial and bronchiolar epithelium, peribronchiolar and perivascular accumulations of lymphocytes, alveolar septal thickening, and collapse. Respiratory syncytial virus was recovered from the respiratory tract of inoculated lambs, and RSV antigen was demonstrated by immunoperoxidase staining of bronchiolar and alveolar epithelial cell in pneumonic lesions of lambs euthanatized on post-inoculation days 5 and 6. Other primary respiratory tract pathogens were not isolated. Clinical signs of respiratory tract illness or respiratory tract lesions did not develop in the in-contact control lamb. Inoculation of the ovine RSV isolate into calves and deer fawns resulted in infection in both species, and at necropsy, pneumonic lesions were present. A mild to moderate respiratory tract illness developed in the calves, but clinical disease was not seen in the fawns. Lung lesions in fawns were similar to those seen in lambs; lesions in calves were characterized by collapse, scattered areas of parenchymal necrosis, and bronchiolitis. Respiratory syncytial virus was reisolated from the lower respiratory tract of inoculated calves and fawns, and immunoperoxidase-positive epithelial cells were seen in pneumonic lesions. Other primary respiratory pathogens were not detected. Respiratory syncytial virus infection was not demonstrable in control animals that were in contact with inoculated animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deposition in the Respiratory Tract of Cattle of Spores of Bacillus subtilis var niger by Inhalation and by Nasal Instillation

Spores of Bacillus subtilis var niger were deposited in the lungs, tracheae and nasal cavities of four calves by aerosol inhalation and in three calves by intranasal instillation. From each calf 20 specimens of lung tissue, each weighing one gm, three of trachea and three of nasal mucosa were examined for spore content. The average numbers of spores per gm of lung tissue from animals exposed to aerosols were 3.05 and 4.84, 2.35 and 2.02 x 10⁴. Lungs from animals exposed intranasally contained only 747, 62 and 1424 spores per gm of tissue respectively. Animals exposed intranasally had a hundred to a thousand fold more spores on nasal mucosa than animals exposed by aerosol and the latter had a thousand fold more spores on tracheal mucosa than calves exposed intranasally. Aerosol inhalation exposed the lung and trachea more densely and uniformly than did intranasal instillation.     

Evidence that blood-borne infection is involved in the pathogenesis of bovine pneumonic pasteurellosis

Five calves were inoculated intravenously with 10(8) colony forming units (cfu) of Pasteurella haemolytica A1; the mean score for pneumonic consolidation 3 days post-inoculation was 28%, and the mean clinical score was 7.8. Five calves inoculated intratracheally with 10(9) cfu of the same strain of P. haemolytica had comparable scores (34% and 8.8). Histological lesions of fibrinous pneumonia were similar in all calves. P. haemolytica was recovered from all but one of the affected lungs. From one calf killed in extremis 3 hours after intravenous inoculation, numbers of bacteria recovered from lung were 1,000-fold greater than from liver and spleen. A similar difference in bacterial numbers was also obtained from a gnotobiotic calf killed in extremis, 12 hours after intravenous inoculation of 10(8) cfu P. haemolytica. Evidence from these experiments supports the hypothesis that the blood-borne route is important in the pathogenesis of bovine pneumonic pasteurellosis.     

Influence of recombinant bovine interferon gamma and dexamethasone on pneumonia attributable to Haemophilus somnus in calves

The influence of recombinant bovine interferon gamma (rBoIFN-gamma) treatment on resistance of clinically normal and dexamethasone-treated calves to Haemophilus somnus infection was evaluated. Four groups of 6 calves each were treated with saline solution (controls), dexamethasone (0.04 mg/kg of body weight/for 3 days), rBoIFN-gamma (2 micrograms/kg for 2 days), or dexamethasone and rBoIFN-gamma (aforementioned dosages). All treatments were started 24 hours before intrabronchial challenge exposure with 5 x 10(9) colony-forming units of H somnus. Rectal temperature and WBC count were monitored daily. Two of the dexamethasone-treated calves died of pneumonia 4 days after challenge exposure and were necropsied. All other calves were euthanatized and necropsied 7 days after challenge exposure. All calves had pneumonia of variable intensity. Dexamethasone-treated calves had increased volume of pneumonic lung (P less than 0.05) and increased severity of pneumonia, compared with control calves. Recombinant bovine interferon gamma treatment resulted in reduction in pneumonic lung volume and severity of pneumonia in dexamethasone-treated calves (P less than 0.05), although it did not influence severity of pneumonia in nondexamethasone-treated calves.     

Respiratory syncytial virus pneumonia in young calves: clinical and pathologic findings

Nine young calves given respiratory syncytial virus by a combined intranasal and intratracheal route developed a severe respiratory tract disease in which coughing, tachypnea, and hyperpnea were prominent clinical features. Calves were euthanatized on postinoculation (initial) days (PID) 1 to 13. At necropsy, large areas of consolidation were present in the cranial, middle, accessory, and cranial parts of the caudal lung lobes of calves killed between PID 4 and 13. Histopathologic examination revealed widespread and severe lesions in small bronchi, bronchioli, and alveoli. Multinucleate epithelial syncytia on bronchiolar and alveolar walls, many containing eosinophilic intracytoplasmic inclusion bodies, were present in the lungs of calves killed on PID 4, 5, and 6. Necrosis and epithelial loss, hyperplasia, and metaplasia were also observed in the epithelium of small bronchi and bronchioli. The lumina of these airways were occluded to varying degrees with exudate. Exudate was present within alveoli, and interalveolar septa were markedly thickened. Collapse of the thickened septa produced large areas where alveolar air spaces were totally obliterated. Repair was evident in the lungs of calves killed at PID 10 and 13 with reepithelialization of damaged bronchiolar mucosa, organization of bronchiolar exudate leading to bronchiolitis obliterans, and peribronchial and peribronchiolar fibrosis. Inoculation of 3 calves by an intranasal route alone produced a less severe clinical disease with only minimal lesions present at necropsy.     

Experimental bovine respiratory tract disease with Haemophilus somnus

Eight calves were inoculated into the bronchus with H. somnus. Thirteen calves were inoculated with bovine respiratory syncytial virus (BRSV) and 8 days later with H. somnus. All calves developed necrotizing, suppurative, lobular bronchopneumonia and pleuritis. Clinical signs of disease and pneumonic lesions were significantly more severe in calves that were sequentially inoculated with BRSV followed by H. somnus. Pneumonic lesions in the inoculated calves were similar to those described for naturally occurring H. somnus-associated respiratory tract disease. Control calves inoculated with BRSV alone or sham-inoculated with medium did not develop clinical signs of respiratory tract disease. The BRSV-inoculated control calves developed minimal pneumonic lesions.     

Vaccination studies against experimental bovine Pasteurella pneumonia.

Vaccination-challenge experiments were conducted in colostrum-deprived calves to evaluate the efficacy of Pasteurella bacterins and vaccines against experimental pneumonic pasteurellosis. Calves were vaccinated with formalin-killed bacterins and live vaccines, then challenge exposed intratracheally with P. haemolytica or P. multocida. Infectious bovine rhinotracheitis virus was inoculated intranasally three to four days prior to P. haemolytica challenge-exposure. All calves were examined for macroscopic and microscopic lesions after being found dead or following euthanasia four to seven days after challenge exposure with the bacterial pathogen. Clinical, hematological, and pathological responses to challenge exposure in aluminum hydroxide absorbed P. haemolytica and P. multocida bacterin-treated calves were consistent with the pneumonic lesions of pulmonary pasteurellosis in the control calves. An oil-adjuvanted P. haemolytica bacterin limited clinical and pathological responses in the affected calves whereas a P. multocida oil-adjuvanted bacterin did not. Both clinical and pathological responses to challenge exposure in calves vaccinated with live Pasteurella vaccines were less severe than those of the control calves. Vaccine effectiveness appeared to be dose dependent.