Experimentally induced pneumonic pasteurellosis: dose-response relationships and protection against natural reinfection in calves

Calves were inoculated intranasally with 2 X 10(6.2) tissue culture infective doses of infectious bovine rhinotracheitis virus, followed in 7 days by intratracheal inoculations with 1 of 4 challenge doses of pathogenic Pasteurella haemolytica. Severity and duration of the ensuing clinical signs of respiratory tract disease were correlated with the challenge dose of bacteria. Calves given 1 X 10(6) colony-forming units (CFU) of bacteria did not develop reliable clinical evidence of disease, whereas those given 1 X 10(8) CFU or 1 X 10(10) CFU of bacteria developed clinical signs of pneumonic pasteurellosis within 12 to 24 hours of bacterial challenge. Severity of clinical signs was equal at the 10(8) and 10(10) doses of bacteria, but duration of clinical signs was greater in calves given the 10(10) dose. Calves given 1 X 10(12) CFU of bacteria developed relatively severe respiratory tract disease in excess of what was necessary for positive clinical detection. Positive correlations were found between the bacterial challenge dose and the height and duration of increased rectal temperature, amount and duration of increases in ocular and nasal discharges, and the subjective evaluation of depressed attitude and appetite. Correlations were not found between challenge dose and respiratory rate or character, or between challenge dose and complete blood cell count. Convalescent calves were resistant to naturally occurring pneumonic pasteurellosis, which caused severe disease in nontreated calves. Adverse effects of P haemolytica were not observed after the first 4 to 15 days after bacterial administration; however, the bacteria were isolated from nasal secretions of convalescent calves 89 to 116 days after bacterial inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pestivirus in cattle: experimentally induced persistent infection in calves

Twenty-two heifers were infected intranasally with non-cytopathic bovine viral diarrhoea virus (BVDV) between days 74 and 82 of pregnancy. All animals had developed serum antibodies against BVDV 5 weeks later. No clinical effects were seen in the heifers, and they all delivered a live calf. The newborn calves were generally small, appeared unthrifty as typical 'poor doers', and some developed secondary infections with diarrhoea and signs of respiratory disease. Eighteen of the 22 calves were born without antibodies against BVDV and were persistently infected (PI) with the virus. One was weak at birth and died the following day. Four calves were born with serum antibodies against BVDV and with no detectable virus. Three of these showed signs and/or pathological changes indicating disease in the central nervous system. Otherwise, there were no obvious clinical differences between these calves and the PI calves, nor were there any apparent significant differences in blood parameters between these groups. In general, the calves showed low gamma-globulin values and thrombocytopaenia, but moderately increased fibrinogen values and relatively normal lymphocyte numbers.     

Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination.

The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the outbreak. The clinical signs comprised nasal discharge, pyrexia, cough and increased respiratory rates. A total of 28 calves died in the 2 herds. The laboratory investigations revealed that BRSV was involved and probably initiated both outbreaks. Furthermore, the serological results suggested that the vaccine induced only sparse levels of antibodies probably due to the presence of maternally derived antibodies at the time of vaccination. Necropsy findings in 5 calves revealed changes typical for infectious pneumonia with involvement of BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish beef herds failed to protect the calves against severe or even fatal BRSV mediated respiratory disease 2 months later.     

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.     

Clinical signs following experimental lungworm infection and natural bovine respiratory syncytial virus infection in calves

Similar clinical signs have been reported in calves infected either by Dictyocaulus viviparus or bovine respiratory syncytial virus. Three experiments were carried out to establish the clinical picture and the course of the disease in animals with these infections. The clinical signs of calves infected with lungworm included coughing, nasal discharge, tachypnoea, abdominal breathing and pyrexia, and auscultation of their lungs revealed increased bronchial sounds. Similar signs were also observed after infection with bovine respiratory syncytial virus, but the signs were more acute and resolved more rapidly than in animals infected with lungworm larvae. Calves infected with lungworm had more serious clinical signs after infection with bovine respiratory syncytial virus than calves, which were not infected with lungworm.     

An unusual outbreak of malignant catarrhal fever in a beef herd in Israel

Malignant catarrhal fever (MCF. corrizza contagiosa) is an invariably fatal communicable disease in cattle, whose causative agent is the ovine herpes virus-2, or the alcelaphine herpes virus-1. In one feed-lot family farm, 34 calves out of 100 became ill at the rate of one to four calves per week, and all of them subsequently died over a period of 4 months. Most of the initial cases were manifested clinically as the head and eye form, but most of the entire clinical spectrum of forms (the respiratory, intestinal and nervous forms) characteristic for MCF were observed as this epidemic progressed. Very few calves died without showing any specific signs of MCF. Pathological examinations revealed characteristic obliterative arteriovasculitis in the brain of calves with nervous signs, typical of MCF. Polymerase chain reaction (PCR) testing revealed 100% homology between the 238 bp hemi-nested PCR fragment and the ovine herpes virus-2 sequences. Based on the clinical signs, epidemiological data, pathological, and histopathological findings, and the PCR results, it was concluded that MCF occurred on the farm. The fact that sheep and goats were housed in close proximity on the same farm reinforced this diagnosis.     

Correlation of a disease scoring system with arterial PO2 values in respiratory syncytial virus infection in calves

The mean arterial PO2 value measured in blood obtained by puncture of the brachial artery of 20 calves with acute clinical signs of a bovine respiratory syncytial virus (BRSV) infection was 8.4 +/- 1.9 kPa. The values differed significantly from arterial PO2 values of eleven healthy calves (mean 14.2 +/- 1.5 kPa). A disease scoring system is presented based on the type of respiration and the findings on auscultation. A high correlation (r = -0.87) was found between disease scores and arterial PO2 values. This indicates that the described disease scoring system can be a useful tool in the evaluation of the severity and course of BRSV infections in calves, and could be used for evaluating the efficacy of BRSV vaccines in the field. The course of disease was studied in 127 calves with clinical signs of serologically proven BRSV infection. Animals with mild respiratory signs during the acute phase of disease remained free of severe respiratory problems until the end of a 35-day examination period. Mean disease scores indicated that animals with severe signs in the acute phase often developed persistent respiratory problems.     

Comparative evaluation of ultrasonography and lung function testing with the clinical signs and pathology of calves inoculated experimentally with Pasteurella multocida

Seventeen calves were inoculated intratracheally with Pasteurella multocida 0 on three consecutive days with 10 ml of an inoculum containing 10(9) colony forming units/ml per day per calf. Before the first inoculation and 24 hours after the third, each calf was examined non-invasively by means of a clinical examination, chest ultrasonography, and impulse oscillometry to measure the impedance of the respiratory system. The inoculation of P multocida caused fever and a significant increase in respiratory rate and a decrease in tidal volume. There were also significant changes in the ultrasonographic results and in the impedance of the respiratory system. The percentage of the total surface area of the lungs showing pathological changes when the calves were euthanased 48 hours after the third inoculation ranged from 0.4 to 39 per cent. There were statistically significant correlations between the ultrasound scores and the pathological findings and between the ultrasound scores and the respiratory rate and tidal volume. The changes in the impedance of the respiratory system were not correlated with either the ultrasonographic or the pathological findings.     

The relationship between clinical signs of respiratory system disorders and lung lesions at slaughter in veal calves

The presence and severity of lung lesions recorded post-mortem is commonly used as an indicator to assess the prevalence of respiratory problems in batches of bovines. In the context of a welfare monitoring based on on-farm measures, the recording of clinical signs on calves at the farm would be more convenient than the recording of lung lesions at slaughter. The aim of the present study was to investigate the relationship between clinical respiratory signs at farm and post-mortem analyses of lung lesions observed at slaughter in veal calves. If clinical signs were a good predictor of lung lesions it could be possible to integrate only those measures in a welfare monitoring system. One-hundred-and-seventy-four batches of calves were observed 3 times: at 3 and 13 weeks after arrival of the calves at the unit and at 2 weeks before slaughter. For each batch a maximum of 300 calves was observed and the proportions of calves showing abnormal breathing, nasal discharge and coughing were recorded. Post-mortem inspection was carried out on a sample of lungs belonging to calves from the observed batches. Each examined lung was classified according to a 4-point scale for pneumonia from healthy lung (score 0) to severe lesions (score 3). The clinical signs recorded infra vitam were significantly correlated with moderate and severe lung lesions for observations at 13 weeks and 2 weeks before slaughter and the level of the correlation was highly variable (r(sp) from 0.16 to 0.40). Receiver operating characteristic (ROC) curves were created and the area under the curves showed that batches with a high proportion of lungs with moderate or severe lesions could not be accurately detected by the three clinical signs of respiratory disorders. These results suggest that both clinical signs and post-mortem inspection of lung lesions must be included in a welfare monitoring schemes for veal calves.     

Clenbuterol hydrochloride in calves with a natural bovine respiratory syncytial virus infection

The effect of clenbuterol hydrochloride on the course of disease in calves with a natural bovine respiratory syncytial virus infection was examined. Six calves (three to nine months of age) originating from four herds with respiratory tract disease and serological evidence of a bovine respiratory syncytial virus infection were used in this study. The calves were injected intravenously with clenbuterol hydrochloride. The effect of clenbuterol on the course of disease was measured using the PO2 in blood taken from an indwelling canula inserted in the caudal auricular artery and by clinical signs. Clenbuterol did not improve clinical signs. After clenbuterol administration arterial PO2 values decreased significantly in five out of six patients. Six to eight hours after medication the mean arterial PO2 values were higher than initial values. The moderate positive effect of clenbuterol after six to eight hours may be caused by enhancing ciliary activity and by the secretolytic activity of clenbuterol.     

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.     

Antibiotic disposition in experimental pneumonic pasteurellosis: gentamicin and tylosin.

The effects of severe respiratory disease on the disposition of antibiotics were evaluated using two drugs chosen because of their widely differing solubility characteristics. The experiments were carried out in series, using five calves for each drug. The drugs were given to seven week old calves before and after induction of pneumonia by bilateral intrapulmonary administration of 3 mL of 5 X 10(7) colony forming units of Pasteurella haemolytica. Following inoculation, the calves developed clinical signs of pneumonia and were given gentamicin (5 mg/kg) or tylosin (10 mg/kg) 48, 60 and 72 hours after Pasteurella administration. There was a statistically significant decrease in distribution rate but not elimination rate of gentamicin. For tylosin, there was a significant increase in elimination rate. These results indicate the kinetics of tylosin but not gentamicin are sufficiently altered as to support a need for increased frequency of administration with severe respiratory disease in calves.     

Correlation of a disease scoring system with arterial PO2 values in respiratory syncytial virus infection in calves

Summary

The mean arterial PO₂ value measured in blood obtained by puncture of the brachial artery of 20 calves with acute clinical signs of a bovine respiratory syncytial virus (BRSV) infection was 8.4 + 1.9 kPa, The values differed significantly from arterial PO₂ values of eleven healthy calves (mean 14.2 ± 1.5 kPa).

A disease scoring system is presented based on the type of respiration and the findings on auscultation. A high correlation (r = ‐0.87) was found between disease scores and arterial PO₂ values. This indicates that the described disease scoring system can be a useful tool in the evaluation of the severity and course of BRSV infections in calves, and could be used for evaluating the efficacy of BRS V vaccines in the field. The course of disease was studied in 127 calves with clinical signs of serologically proven BRSV infection. Animals with mild respiratory signs during the acute phase of disease remained free of severe respiratory problems until the end of a 35‐day examination period. Mean disease scores indicated that animals with severe signs in the acute phase often developed persistent respiratory problems.     

Effect of infection with bovine respiratory syncytial virus on pulmonary clearance of an inhaled antigen in calves

OBJECTIVE: To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves. ANIMALS: Eleven 6- to 8-week-old Holstein bull calves. PROCEDURES: Aerosolized (99m)technetium ((99m)Tc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and (99m)Tc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined. RESULTS: Clearance of (99m)Tc-DTPA was significantly increased during BRSV infection; clearance of (99m)Tc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of (99m)Tc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of (99m)Tc-OA were detected at time points when pulmonary clearance of (99m)Tc-OA was most delayed. CONCLUSIONS AND CLINICAL RELEVANCE: BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease. IMPACT FOR HUMAN MEDICINE: Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.     

Experimental infection of calves with bovine respiratory syncytial virus (Quebec strain).

An experiment was designed to evaluate the clinical, haematological, viral and serological aspects of bovine respiratory syncytial virus infection in calves. Eleven calves were inoculated intranasally with bovine respiratory syncytial virus (Quebec strain) in aerosol. Clinical, haemotological and serological responses of the calves and virus shedding were monitored. The experimentally infected animals manifested moderate to severe signs of respiratory disease. The parameters used to evaluate the severity of the disease included ocular discharge, conjunctivitis, lung sounds, nasal discharge, pyrexia and leukopenia. The animals were scored accordingly (scale infected 70.8-148.5, control 22-29.3). Highest disease scores were observed between day 6-9 after infection. Virological and serological assessment demonstrated that the observed clinical picture was due to bovine respiratory syncytial virus infection.     

Radiographic and radionuclide lung perfusion imaging in healthy calves and calves naturally infected with bovine respiratory syncytial virus.

Nine calves between three and 18 weeks old with serologically confirmed natural bovine respiratory syncytial virus infection were examined clinically, radiographically and by radionuclide lung perfusion imaging. The results were compared with those from seven healthy calves. The diseased calves were euthanased and examined pathologically, virologically and bacteriologically. The clinical signs indicated that the disease was in an acute stage. Radiography of the diseased animals revealed cysts, corresponding morphologically with bullous emphysema, and infiltrations roughly corresponding in distribution with atelectatic and, or, pneumonic areas. Radionuclide lung perfusion imaging revealed no perfusion shifts between the left and right lungs and a normal perfusion pattern in five of the nine diseased calves. The abnormalities in the perfusion patterns of three calves were probably caused by anatomical disorders such as cysts and pleural adhesions, but no cause of the abnormality could be found in one calf. These findings suggest that in calves infected with bovine respiratory syncytial virus, the normal perfusion pattern is maintained until anatomical disorders occur. The pathological examination and radiography revealed that the cranioventral lung fields were particularly poorly ventilated. This finding and the normal perfusion pattern indicate that these parts of the lungs are probably the sites where shuntings and perfusion-ventilation mismatchings occur.     

Evaluation of severe disease induced by aerosol inoculation of calves with bovine respiratory syncytial virus

OBJECTIVE: To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. ANIMALS: 25 male Holstein calves, 8 to 16 weeks old. PROCEDURE: 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. RESULTS: Cumulative incidence of cough, harsh lung sounds, adventitious sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying degrees of necrotizing and proliferative bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. CONCLUSION AND CLINICAL RELEVANCE: Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.     

Effects of Jatropha curcas on calves.

Jatropha curcas seed was fed to six calves at doses of 2.5, 1 and 0.25 g/kg once and to two other calves at 0.025 g/kg up to 14 days. The onset of toxic manifestations in the six calves was rapid and death occurred within 19 hours of administration. The two calves that received daily the lowest dose of J. curcas showed signs of poisoning and died within 10 to 14 days. The clinical signs of diarrhoea, dyspnoea, dehydration and loss of condition were well correlated with the pathological findings. There was an increase in aspartate aminotransferase, ammonia and potassium and a decrease in total protein and calcium in the serum of jatropha-poisoned calves.     

Seroepizootiologic study of bovine respiratory syncytial virus in a dairy herd

A 16-month seroepizootiologic study of bovine respiratory syncytial virus (BRSV) infection was conducted in a dairy herd. Results indicated that antibodies to BRSV present in serum from newborn calves were derived through the ingestion of colostrum. This passive immunity in calves became undetectable in an average of 99 days (SD = 36.5; range = 30 to 208 days). Two epizootics of respiratory tract disease occurred during the study period, and an association with BRSV was demonstrated in both epizootics. In the 2 epizootics, clinical signs of respiratory tract disease were only mildly to moderately severe, with no mortality or evidence of chronic pneumonia occurring. Seemingly, the passive immunity failed to protect calves from infection and disease caused by BRSV. Additionally, it was observed that if active immunity was induced by infection with BRSV, this immunity protected from the development of clinical disease, but not from reinfection upon subsequent exposures to BRSV.