Experimental reproduction of respiratory tract disease with bovine respiratory syncytial virus

An experiment was conducted to reproduce respiratory tract disease with bovine respiratory syncytial virus (BRSV) in one-month-old, colostrum-fed calves. The hypothesized role of viral hypersensitivity and persistent infection in the pathogenesis of BRSV pneumonia was also investigated. For BRSV inoculation a field isolate of BRSV, at the fifth passage level in cell culture, was administered by a combined respiratory tract route (intranasal and intratracheal) for four consecutive days. Four groups of calves were utilized as follows: Group I, 6 calves sham inoculated with uninfected tissue culture fluid and necropsied 21 days after the last inoculation; Group II, 6 calves inoculated with BRSV and necropsied at the time of maximal clinical response (4-6 days after the last inoculation); Group III, 6 calves inoculated with BRSV and necropsied at 21 days after the last inoculation; Group IV, 6 calves inoculated with BRSV, rechallenged with BRSV 10 days after initial exposure, and necropsied at 21 days after the initial inoculation. Clinical response was evaluated by daily monitoring of body temperature, heart rate, respiratory rate, arterial blood gas tensions, hematocrit, total protein, white blood cell count, and fibrinogen. Calves were necropsied and pulmonary surface lesions were quantitated by computer digitization. Viral pneumonia was reporduced in each principal group. Lesions were most extensive in Group II. Disease was not apparent in Group I (controls). Significant differences (p less than 0.05) in body temperature, heart rate, respiratory rate, arterial oxygen tension, and pneumonic surface area were demonstrated between control and infected calves. Results indicate that severe disease and lesions can be induced by BRSV in one-month-old calves that were colostrum-fed and seropositive to BRSV. BRSV rechallenge had minimal effect on disease progression. Based on clinical and pathological response, results did not support viral hypersensitivity or persistent infection as pathogenetic mechanisms of BRSV pneumonia.     

Immune mechanisms of pathogenetic synergy in concurrent bovine pulmonary infection with Haemophilus somnus and bovine respiratory syncytial virus

Bovine respiratory syncytial virus (BRSV) and Haemophilus somnus are two bovine respiratory pathogens that cause disease singly or as part of a polymicrobial infection. BRSV infection is often associated with a predisposition towards production of a T helper type 2 (Th2) response and IgE production. In contrast, an IgG2 response to H. somnus has been shown to be most important for recovery. An experiment was performed to evaluate the hypothesis that infection with H. somnus on day 6 of experimental BRSV infection would result in disease enhancement and potentially an altered immune response when compared with single infection. Three groups of calves were either dually infected or singly infected with H. somnus or BRSV. Serum and bronchoalveolar lavage fluid (BALF) pathogen specific IgG1, IgG2, IgE, and IgA responses were evaluated by ELISA. TaqMan RT-PCR was used to examine cytokine gene expression by PBMC and BAL cells. Clinical signs were evaluated for 28 days after BRSV infection, followed by necropsy and histological examination of the lungs. In dually infected calves, disease was significantly more severe, H. somnus was isolated from the lungs at necropsy, and high IgE and IgG responses were detected to H. somnus antigens. Cytokine profiles on day 27 were elevated in dually infected calves, but did not reflect a skewed profile. These results contrasted with singly infected calves that were essentially normal by day 10 of infection and lacked both lung pathology and the presence of H. somnus in the lung at necropsy. The increase in IgE antibodies specific for antigens of H. somnus presents a possible mechanism for pathogenesis of the disease enhancement.     

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)     

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.     

Efficacy of an inactivated respiratory syncytial virus vaccine in calves.

OBJECTIVE: To determine whether an inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from infection with virulent BRSV. DESIGN: Randomized controlled trial. ANIMALS: 27 nine-week-old calves seronegative for BRSV exposure. PROCEDURE: Group-1 calves (n = 9) were not vaccinated. Group-2 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing a minimum immunizing dose of antigen. Group-3 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing an amount of antigen similar to that in a commercial vaccine. All calves were challenged with virulent BRSV on day 42. Clinical signs and immune responses were monitored for 8 days after challenge. Calves were euthanatized on day 50, and lungs were examined for lesions. RESULTS: Vaccination elicited increases in BRSV-specific IgG and virus neutralizing antibody titers and in production of interferon-gamma. Virus neutralizing antibody titers were consistently less than IgG titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, whereas vaccinated calves had less severe signs of clinical disease and less extensive pulmonary lesions. The percentage of vaccinated calves that shed virus in nasal secretions was significantly lower than the percentage of control calves that did, and peak viral titer was lower for vaccinated than for control calves. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus and decreased the severity of pulmonary lesions. Efficacy was similar to that reported for modified-live BRSV vaccines.     

Efficacy of a saponin-adjuvanted inactivated respiratory syncytial virus vaccine in calves

The objective of this study was to determine whether a commercially available, saponin-adjuvanted, inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from experimental infection with virulent BRSV. This was a randomized controlled trial comprising 14, 8- to 9-week-old calves seronegative for BRSV Group 1 calves (n = 8) were not vaccinated and group 2 calves (n = 6) were vaccinated on days 0 and 19 with an inactivated BRSV vaccine. All calves were challenged with virulent BRSV on day 46. Clinical signs, arterial PO2, and immune responses were monitored after challenge. Calves were euthanatized on day 54 (8 d after challenge) and lungs were examined for lesions. Vaccination elicited increases in BRSV-specific immunoglobulin (Ig) G and virus neutralizing antibody titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, but no signs of clinical disease and minimal or no pulmonary lesions in vaccinated calves. Arterial blood oxygen values on day 53 (7 d after challenge) in control calves were significantly lower than those in vaccinated calves, which remained within normal limits. Control calves shed BRSV for several days after challenge, whereas BRSV was not detected on deep nasal swabs from vaccinated calves. In summary, the results indicated that this inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus 27 d after vaccination and significantly decreased the prevalence and severity of pulmonary lesions. Efficacy was similar to that reported for other commercial inactivated and modified-live BRSV vaccines.     

Specificity of IgG and IgE antibody responses to Haemophilus somnus infection of calves

Haemophilus somnus is an important cause of bovine respiratory disease and septicemia with all it's sequelae. The role of immune responses in protection and immunopathogenesis is not well understood. We showed that infection with bovine respiratory syncytial virus (BRSV) 6 days before H. somnus increased clinical scores and levels of IgE antibody to H. somnus over that of infection with H. somnus alone. To determine whether antigenic specificity of IgE responses differed from IgG responses, Western blots were done with sera from the infected calves, at 0 time and at 21 days post infection. Thus each calf was its own control. IgG antibodies recognized primarily a 40 kDa outer membrane protein (OMP) in whole cell H. somnus preparations and a 270 kDa immunoglobulin binding protein (IgBPs) in culture supernatants but generally not the 41 kDa major OMP (MOMP). IgE antibodies recognized primarily the 41 kDa MOMP in whole cell pellet preparations. Results were consistent among calves. With culture supernatants, IgE antibodies recognized both the 270 kDa IgBPs and the MOMP. Since some H. somnus strains from asymptomatic carriers (including strain 129Pt), do not have IgBPs and express a truncated MOMP (33 kDa rather than 41 kDa), reaction of strain 129Pt cells with serum from calves infected with H. somnus or BRSV and H. somnus was studied. IgE did not react with the truncated MOMP even at much lower (1:100) dilutions than in Western blots with virulent strain 2336 (serum dilution of 1:500). Reactions of IgE with the 40 and 78 kDa antigens in strain 129Pt were noted but since the major reactivities with the IgBPs and the MOMP were not detected, this strain may be useful for inducing protective rather than immunopathogenic responses.     

Response of calves to challenge exposure with virulent bovine respiratory syncytial virus following intranasal administration of vaccines formulated for parenteral administration

OBJECTIVE: To determine whether single-fraction and combination modified-live bovine respiratory syncytial virus (BRSV) vaccines commercially licensed for parenteral administration could stimulate protective immunity in calves after intranasal administration. DESIGN: Randomized controlled trial. ANIMALS: 39 calves. PROCEDURES: Calves were separated from dams at birth, fed colostrum with a minimal concentration of antibodies against BRSV, and maintained in isolation. In 2 preliminary experiments, 9-week-old calves received 1 (n = 3) or 2 (3) doses of a single-component, modified-live BRSV vaccine or no vaccine (8 control calves in each experiment), and were challenged with BRSV 21 days after vaccination. In a third experiment, 2-week-old calves received combination modified-live virus (MLV) vaccines with or without BRSV and calves were challenged with BRSV 8 days later. Calves were euthanized, and lung lesions were measured. Immune responses, including serum and nasal antibody and nasal interferon-alpha concentrations, were assessed. RESULTS: BRSV challenge induced signs of severe clinical respiratory tract disease, including death and pulmonary lesions in unvaccinated calves and in calves that received a combination viral vaccine without BRSV. Pulmonary lesions were significantly less severe in BRSV-challenged calves that received single or combination BRSV vaccines. The proportion of calves that shed virus and the peak virus titer was decreased, compared with control calves. Protection was associated with mucosal IgA antibody responses after challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Single and combination BRSV vaccines administered intranasally provided clinical protection and sparing of pulmonary tissue similar to that detected in response to parenteral delivery of combination MLV and inactivated BRSV vaccines previously assessed in the same challenge model.     

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.     

Virulence differences among three strains of Haemophilus somnus following intratracheal inoculation of calves.

Pneumonia was induced in four month old Holstein calves by intratracheal inoculation of 1 x 10(9) colony forming units of Haemophilus somnus. Twenty calves were divided into four groups of five and challenged with a pneumonic strain (Group 1), an encephalitic strain (Group 2), a preputial strain (Group 3), or a placebo (Group 4). The clinical score, neutrophil count, respiratory rate, and temperature were significantly increased in group 1 by day 1 postinoculation (P less than 0.05) and maintained until day 6 postinoculation (P less than 0.05). The macroscopic pathological changes were significantly greater in group 1 (P less than 0.05). Haemophilus somnus was consistently isolated from pneumonic tissue of group 1 only. Groups 2 and 3 had mild transient increases in all parameters measured and macroscopically only small focal lesions were present. It is concluded that virulence differences exist between H. somnus strains following intratracheal challenge of bovine lungs.     

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)     

Inhibition of priming for bovine respiratory syncytial virus-specific protective immune responses following parenteral vaccination of passively immune calves

The effect of maternal antibodies (MatAb) on immunological priming by neonatal parenteral vaccination for bovine respiratory syncytial virus (BRSV) was addressed for the first time in experimental infection in 34 Holstein calves. Both vaccinated and control calves developed moderate to severe respiratory disease characteristic of acute BRSV infection. There were no differences in clinical signs, BRSV shed, arterial oxygen concentrations, or mortality between vaccinated and control calves after BRSV challenge approximately 11 wk after vaccination. There were no anamnestic antibody or cytokine responses in the vaccinates after challenge. Lung lesions were extensive in both groups, and although there was a statistically significant (P = 0.05) difference between groups, this difference was considered not biologically significant. These data indicate that stimulation of protective immune responses was inhibited by maternal antibodies when a combination modified-live BRSV vaccine was administered parenterally to young passively immune calves. Alternate routes of administration or different vaccine formulations should be used to successfully immunize young calves with good passive antibody transfer.     

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.     

Haemophilus somnus as a bacterial cause of pneumonia in buffalo calves in Egypt.

Haemophilus (H.) somnus strains were isolated from nasopharyngeal swabs collected from buffalo calves showing respiratory symptoms as well from pneumonic lung tissue samples, the incidence being 4.7% and 10.4%, respectively. The organism was not recovered from samples obtained from apparently healthy buffalo calves. All isolated strains were highly virulent to mice, causing acute septicaemia and death within 3-5 days from intraperitoneal inoculation with 7.5 x 10(6) viable organisms. All tested strains were resistant to tetracycline and sulphafurazole, but most strains were highly sensitive to gentamicin, ampicillin, penicillin G, and colistin sulphate. H. somnus must not be neglected as a causative agent of respiratory disorders in buffalo calves, in addition to other incriminated organisms.     

Immunoglobulin M-specific enzyme-linked immunosorbent assay for serodiagnosis of bovine respiratory syncytial virus infections

An antibody-capture enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin (Ig) M antibodies to bovine respiratory syncytial virus (BRSV) in cattle was developed. Monoclonal antibody to bovine IgM was used as the catching antibody. The IgM-ELISA was used, as well as a BRSV-specific IgG ELISA to determine the kinetics of IgM and IgG antibody responses to BRSV infections in cattle. High IgM and IgG antibody titers developed after naturally occurring or induced BRSV infection of calves (6 to 7 months old). Induced infection resulted in an IgM response that was first detectable at postinoculation day (PID) 11 reached a maximum at PID 13, and became undetectable again about PID 28. An IgG response also was detected by PID 11. However, a maximum response was not reached before PID 23, and titers remained high (until PID 80). In naturally occurring infection, IgM and IgG responses in calves were observed in the acute phase of epizootics of respiratory tract disease. Patterns of IgM and IgG response curves were similar to those observed in experimentally infected calves. The involvement of BRSV in an epizootic of respiratory tract disease in 8 calves (2 to 3 weeks old) was demonstrated by the detection of BRSV in several lung lavage samples. All calves had existing IgG antibodies to BRSV which were interpreted to be maternally derived. None of the calves responded with an increase in IgG antibody titer. However, a weak but distinct BRSV IgM antibody response occurred in 6 calves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Culture-positive persistence and serum agglutinating antibody response after intrauterine inoculation of Haemophilus somnus in virgin heifers

Viable Haemophilus somnus of reproductive tract origin (OSU-1167) was inoculated transcervically into the uterus of 6 virgin heifers. Five heifers were sham-inoculated (intrauterine) with sterile mycoplasmal medium and served as controls. After inoculation and observation, all heifers had nasal and vaginal vestibular swab specimens and serum obtained periodically for 44 days. Signs of systemic illness were not detected. On the day after inoculation, all inoculated heifers had signs of vulvovaginitis, whereas none of the control heifers had similar signs (P less than 0.002). Haemophilus somnus was not isolated from any nasal or vaginal vestibular swab specimens obtained before inoculation or from any nasal swab specimens obtained after inoculation. During the 44 days after inoculation, H somnus was isolated from 25 of 54 vestibular specimens obtained from inoculated heifers and from 3 of 45 specimens obtained from controls (P less than 0.02). Vulvovaginal lesions were associated with vestibular isolation of H somnus in 23 of 25 (92%) such isolations from inoculated heifers; lesions were never associated with concurrent isolation of H somnus in controls. All heifers had H somnus microagglutination test (MAT) titer less than or equal to 256 against a commercially prepared H somnus antigen at the beginning of the study. Considered as groups, neither inoculated nor control heifers achieved fourfold increases in MAT titer during the 44 days after inoculation. When compared by day of sample collection, inoculated heifers did have significantly (P less than 0.04) lower geometric mean titer at 7 days after inoculation than did control heifers when tested by use of a commercially prepared antigen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence and specificity of antibodies to bovine respiratory syncytial virus in sera from feedlot and range cattle

The specificity of serum antibodies for the polypeptides of bovine respiratory syncytial virus (BRSV) was examined, using sera obtained from feedlot and range cattle. Test results in sera from feedlot cattle indicated a 60% rate of seroconversion and 95% seropositivity to BRSV, associated with lack of clinical signs indicative of respiratory tract disease. Exposure to other common respiratory tract viruses also was high (greater than or equal to 92% to bovine herpesvirus type 1, bovine viral diarrhea virus, and para-influenza virus type 3). Test results in sera from range cattle indicated BRSV seropositive rates of 28% in calves, 49% in yearling cattle, and 70% in mature cows; clinical signs of respiratory tract disease were not observed in these cattle. Antibodies to BRSV in sera from cattle in both environments reacted predominantly with polypeptides of molecular weight 80,000 through 85,000, 40,000, and 28,000. Reactivity to a glycoprotein of molecular weight between 43,000 and 44,000 and to several glycopolypeptides of smaller molecular weight increased in serum specimens obtained from feedlot cattle between time of entry into the feedlot and slaughter.     

Pathological and microbiological studies on pneumonic lungs from Danish calves

During 1 year, the association between microbiological and pathological findings in 72 lungs from calves submitted to the Danish Veterinary Laboratory for diagnostic purposes was studied. All cases were evaluated pathologically and bacteriologically, whereas only 68 cases were examined for the presence of bovine respiratory syncytial virus (BRSV), parainfluenza-3 virus (PI-3 virus) and bovine coronavirus, 62 cases for bovine viral diarrhoea virus (BVD), 45 cases for bovine adenovirus and 51 cases for mycoplasmas. Based on histopathological examination, the cases were diagnosed as fibrinous and/or necrotizing bronchopneumonia, suppurative bronchopneumonia, embolic pneumonia and others. The diagnoses were based on the dominating and most severe lesions in each lung. Haemophilus somnus, Pasteurella multocida, Actinomyces pyogenes, P. haemolytica and BRSV were the most commonly found bacterial and viral lung pathogens, respectively. Pasteurella spp. and H. somnus were often associated with the more severe fibrinonecrotizing type of bronchopneumonia, whereas BRSV was primarily detected in cases of suppurative bronchopneumonia. Mycoplasma bovis was isolated from one case only, whereas M. dispar, M. bovirhinis and Ureaplasma diversum were present, often concomitantly, in the majority of cases. Aspergillus fumigatus was isolated from one case.     

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.     

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.