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An epidemiological study was conducted in a dairy calf rearing unit to assess the relationship between animal characteristics (age, bodyweight and appetite), involvement of viral and bacterial pathogens, biochemical analysis (haptoglobin) as well as the course and clinical outcomes of the Bovine Respiratory Disease Complex (BRDC). In the clinical study, comprehensive data was generated between October 2010 and March 2011 in a clinical pharmacological trial following Good Clinical Practice (GCP) conditions. The study included 104 calves between 12 and 56 days of age which were under permanent observation starting from the time of inclusion in the study. Calves included in the study were suffering from the BRDC and fulfilled preset inclusion criteria (rectal temperature ≥ 40 °C and respiratory score ≥ 1 and attitude score ≥1). Following inclusion, the selected calves were subjected to physical examination at regular intervals as well as comprehensive diagnostics including sampling of materials for bacteriological, serological and biochemical examinations. The clinical symptoms and feed intake of 104 calves were recorded throughout the study and clinical findings were expressed in clinical score values. Trans-tracheal lavages for bacteriological examination were performed before treatment was initiated. Furthermore, paired serum samples were collected for determination of the levels of specific antibodies directed at BHV-1, BRSV, BPIV-3, BVDV and M. bovis. In addition, the acute phase protein ß-haptoglobin was determined in serum samples. After initial specimen collection, animals received a single treatment with a macrolide following the manufacturer’s information. The calves were then closely observed over a period of 22 days. Animals with persistent or relapsing respiratory symptoms and animals which developed a concomitant disease were excluded from the study if they had fulfilled preset exclusion criteria, but data obtained up to the day of exclusion was considered in the present study. At time of exclusion a second trans-tracheal lavage was performed on these animals. Data processing and analysis were carried out with the statistical software package SPSS for Mac, Version 19. From 69.2% (72/104) of the TTL-specimens, bacteria were isolated. In 30.8% (32/104) of the samples no bacteria were cultured. P. multocida was cultured from 31.7% (33/104) of the TTL samples and was therefore the most frequently isolated pathogen. M. haemolytica was cultured from 18.3% (19/104) of the specimens. H. somni was detected in only one sample and M. bovis was not found at all. In 25% (26/104) of the specimens, miscellaneous bacteria (primarily environmental bacteria, which are not known to act as respiratory pathogens) were detected. Repeated trans-tracheal lavages in 22 calves with persistent or relapsing BRDC were positive for bacteriological analysis in 54.5% (12/22). Most commonly, P. multocida was isolated (31.8% (7/22)). In one of those calves, a mixed-infection with M. haemolytica and P. multocida was found. From the lung of one calf with a fatal course of BRDC, P. multocida and M. haemolytica were cultured. In cases in which M. haemolytica was isolated from TTL-specimens, calves demonstrated a significantly lower body weight at inclusion than calves with a TTL positive for P. multocida. In addition, the course of disease was less serious in the latter group of animals. Calves with simultaneous culture of P. multocida and M. haemolytica from TTL specimens revealed a significantly lower milk replacer intake at inclusion than calves with a single infection of either bacterial species. Serological testing showed that 93.3% (97/104) of all tested calves were positive for antibodies directed at BHV-1, 81.7% (85/104) BPIV-3, 77.9% (81/104) BRSV and 73.1% (76/104) BVDV. These antibodies were presumably maternal antibodies. For paired serum samples, only one animal fulfilled criteria of the test for seroconversion (BRSV). 4.8% (5/104) of the animals tested positive for antibodies directed at M. bovis antigen. These were presumably originating from colostral antibody transfer. Calves excluded from the study due to persisting or relapsing BRDC weighed significantly less and showed more severe symptoms on the inclusion date than calves that recovered after a single antibiotic treatment. Within three months of arrival at the calf rearing facility, 56,4% (53/94) of the animals had a relapse of BRDC and needed additional treatment. Of all calves, 13,8% (13/94) required three or more treatments within the three month period. Calves which required just one treatment within this period were significantly older at inclusion and fell sick significantly later after arrival compared to the calves with relapses of BRDC. Furthermore, the body weights of calves requiring at least three treatments were significantly lower on the day of inclusion compared to calves requiring a maximum of two treatments. On the day of inclusion, a day where all included animals were clinically ill with BRDC, less than 60% of the animals had haptoglobin values above the detection threshold.
There was no association demonstrated between the severity of the symptoms and blood serum concentrations of haptoglobin. Nevertheless, animals which recovered following the treatment had significantly lower haptoglobin concentrations on the first and second day following treatment, than those animals which did not recover. Calves requiring three or more treatments had significantly higher haptoglobin concentrations on the inclusion day, than calves only treated once or twice for BRDC. On the day previous to the inclusion date, calves which recovered from BRDC had a significantly higher milk replacer intake compared with their penmates which did not recover. The results of this present study underline the important role of host characteristics and P. multocida and M. haemolytica in the pathogenesis of the BRDC. Disease symptoms related to M. haemolytica infection were more severe than those related to P. multocida. Haptoglobin is neither suitable as an indicator for animals that need to be treated nor for the assessment of the severity of the BRDC. However, haptoglobin might be used as a prognostic tool for the treatment outcome and the likelihood of recurrent disease. Furthermore additional research is needed in this area. The associations between body weight and treatment outcome, as well as body weight and BRDC recurrence highlight the importance of non-infectious factors within the polyfactorial pathogenesis of the BRDC. Within the framework of this study, viruses played a minor role in the pathogenesis. In conclusion, non-infectious factors including stressors like transportation and commingling as well as on-farm conditions impair physical and immunological defense mechanisms and therefore facilitate the bacterial advance and colonization of the lower respiratory tract.