Strength of association between isolation of Pasteurella multocida and consolidation lesions in ovine pneumonic pasteurellosis.

This study investigated the association of Pasteurella multocida isolation and the molecular characteristics of the isolates with the presence of pneumonic lesions in lambs at slaughter to assess its importance as a causative agent of pneumonic pasteurellosis compared with Mannheimia haemolytica. P. multocida was isolated from the 13.9% and 2.7%, and M. haemolytica from the 36.4% and 26.8%, of lungs with and without lesions, respectively (P < 0.05). Both microorganisms were frequently coisolated (23.2% and 12.5% from lungs with and without lesions, respectively). Isolation of P. multocida alone exhibited greater strength of association with pneumonic lesions (OR 11.4; 95% CI 3.2-40.6) than that exhibited by M. haemolytica alone (OR 3.0; 95% CI 1.6-5.4). Cluster analysis grouped the lungs into four clusters characterized by the isolation of M. haemolytica or P. multocida alone (clusters 1 and 4), coisolation of both microorganisms (cluster 3), and isolation of neither (cluster 2). Cluster 4 lungs exhibited higher frequencies of pneumonic lesions (87.5%) and severe (20.8%) and moderate (25.0%) lesions. Lungs coinfected with both pathogens (cluster 3) did not exhibit a higher frequency of severe and moderate consolidation lesions (6.1% and 14.3%, respectively), suggesting that P. multocida and M. haemolytica do not act synergically to cause more severe pneumonic infections. The greater strength of association of P. multocida isolation with pneumonic lesions together with the higher severity of the lesions caused could indicate a greater role played by this pathogen in the aetiopathogenesis of pneumonic pasteurellosis in sheep than is commonly assumed.

Bacterial, PCR and clinico-pathological diagnosis of naturally occurring pneumonic pasturellosis (mannheimiosis) during subtropical climate in sheep.

Mannheimia haemolytica is causative agent of pneumonic pasteurellosis (mannheimiosis) that causes huge economic losses to livestock farmers. We investigated the microbial and clinico-pathological patterns associated with ovine pneumonic pasturellosis during an outbreak. Prior to death, infected sheep revealed clinical signs including dyspnoea, salivation, pyrexia and mucopurulent nasal discharge. Mortality was significantly (p < 0.05) high in young sheep as compared to adults. Necropsy findings revealed presence of froth in trachea, congestion and consolidation of lungs, pulmonary edema, severe pleural adhesions, pericarditis, hemorrhages on mucosa of jejunum and kidneys. Histopathological examination revealed circumscribed and centrally calcified necrotic areas punctuated with chronic inflammatory cells and interstitial pneumonia. Moreover, bronchial epithelial hyperplasia, edema, congestion, mononuclear cell infiltration, thick interlobular septae and peri-vascular cuffing were the striking changes in lungs. Furthermore, lungs showed severe fibrin depositions along with abundant amount of fibrin meshwork on pleura infiltrated with chronic inflammatory cells. Histologically, liver, kidneys and lymph nodes showed degenerative changes. Mannheimia haemolytica and Pasteurella multocida were differentially identified on the basis of culture characteristics and biochemical tests. M. haemolytica was further confirmed by using polymerase chain reaction. From the findings of current study, it is concluded that M. haemolytica is a major respiratory threat in small ruminants that causes severe pneumonic changes in infected animals.

Differences in Virulence Between Bovine-Derived Clinical Isolates of Pasteurella multocida Serotype A from the UK and the USA in a Model of Bovine Pneumonic Pasteurellosis.

The time of onset and subsequent degree and progression of clinical signs, bacterial colonization and tissue pathology during experimental disease induced by intratracheal inoculation of either a UK or USA isolate of Pasteurella multocida serotype A recovered from clinical cases of bovine pneumonia were determined. Calves aged 8 weeks were challenged with 300 ml phosphate buffered saline (PBS) alone (group 1, n = 3, negative control) or containing 7.1 × 10(8) colony forming units (cfu) of UK isolate (group 2, n = 8) or 5.8 × 10(8) cfu of USA isolate (group 3, n = 8). Bronchoalveolar lavage (BAL) at 0, 1 and 4 days post challenge (dpc) and at the time of necropsy examination (7-8 dpc) showed no significant differences between groups 2 and 3 in bacterial numbers recovered. No P. multocida were recovered from group 1 animals. No clinical disease was present in group 1 calves and in group 3 was limited to scour in 1 calf at 1 dpc. All calves in group 2 had reduced food intake at 4-5 dpc, five had periods of dullness, three a mild nasal discharge at 1 dpc, four had mild to substantial respiratory stridor and one was killed at 6 dpc for humane reasons. Rectal temperatures remained about 39°C in group 1 calves, but increased in P. multocida-challenged calves to 40-41°C within 8-12 h of challenge. Significantly (P = 0.01) greater percentages of lung surface area were consolidated in group 2 (mean ± SD, 21 ± 10.1) compared with group 3 (7 ± 8.6) calves. Significantly more extensive and severe histological lesions were present in the lung lobes (P = 0.006) and lymph nodes (P = 0.02) of group 2 compared with group 3 calves. Pleurisy was present in group 2 calves only and no pathology was present in group 1. Pulsed-field gel electrophoresis (PFGE) produced 11 (group 2, UK isolate) or 10 (group 3, USA isolate) bands with differences in banding patterns. Results overall showed that two isolates, distinct geographically and genetically (by PFGE), caused pneumonic pasteurellosis in a single host with significantly different severity of pathology. This information is relevant to the development of novel vaccine control and interpretation of diagnostic results.

Pathology of experimental infection by Pasteurella multocida serotype A: 1 in buffalo calves.

Pasteurella multocida serotype A:3 has been mostly implicated in pneumonic pasteurellosis in ruminants. In contrast, our previous studies have reported that both serotypes A:1 and A:3 were responsible for respiratory diseases in cattle and buffaloes. However, the pathology and pathogenesis of P. multocida serotype A:1 (Pm A:1) infection have not been studied in ruminants. In the present study, 12- to 15-week-old buffalo calves (Bubalus bubalis) infected by Pm A:1 had fibrinous and suppurative bronchopneumonia with focal areas of coagulation necrosis typical of pneumonic pasteurellosis. For the first time, this study reports the lung pathology and pathogenecity of Pm A:1 infection in calves.

In vivo gene expression in Mannheimia haemolytica A1 during a time-course trial in the bovine host.

The objective of this study is to examine the expression of Mannheimia haemolytica genes over time during the early stage of infection. In addition, gene expression at different sites of infection in the bovine host was examined. A time-course experiment was designed to collect pharyngeal swabs and lung washings from the same animals over two time points. Six calves were experimentally challenged with M. haemolytica A1; pharyngeal swabs were collected from all animals 5h post infection. Three calves were euthanized at 6h; pharyngeal swabs were collected from the remaining 3 calves at 12h and the calves were euthanized. Lung washings were recovered from all animals at necropsy. Total RNA was prepared from the pharyngeal swabs and lung washings and primers for eight well characterized virulence-associated genes were used in qRT-PCR to examine mRNA levels. The expression of key virulence genes such as lktA, gcp and tbpB was higher in vivo compared to in vitro with the highest changes observed from 6 to 12h. The expression of lktA and gapA increased while expression of fbpA, gs60, nmaA and tbpB was found to decreased over time in the 6h period. Gene expression profiles in the lungs versus the pharynx also differed, with most genes (fbpA, tbpB, nmaA, gs60, lktA and narP) showing higher expressing in lung washings. This is the first study to follow gene expression by M. haemolytica in the same animal over time during an infection.

Clinicopathological observations in experimental peste des petit ruminants virus and Mannheimia haemolytica A:2 co-infection in goats.

The experiment describes for the first time the clinicopathological features of the co-infection of Peste des petit Ruminants (PPR) virus and Mannheimia haemolytica,in goats. Twenty clinically healthy goats, six months of age were used. 15 goats were infected by intratracheal inoculation of 1ml of pure cultured 106.5 TCID50 PPR virus grown in Baby hamster kidney cell lines, and a week later,1 ml of pure culture (109 CFU) of Mannheimia haemolytica (MH)A2 to study its clinico-pathological features and five goats served as controls. The clinical signs were observed and two goats were euthanized at predetermined intervals for gross examinations, bacteriological, virological and histopathological investigations on tissues collected using standard techniques. The clinical signs were severe and the order of manifestation was anorexia, pyrexia, dyspnea, oculo-nasal discharge, recumbency and death. The lesions observed were severe fibrinous bronchointerstitial pneumonia and pleurisy with thickened alveolar septa, edema and neutrophilic infiltrations of the interstitium with giant cells. There was also marked erosive stomatitis and acute enteritis. The average percentage lung consolidation for the infection was 7.01% and the right lung was more affected (p<0.05) while the overall mortality was 33.3%. MHA:2 and PPR virus were re-isolated from the lungs. The clinicopathological features observed showed that goats were susceptible to co- infection of PPR and Mannheimiosis which was severe and fatal. The data should help veterinarians and other medical experts to recognize cases of bacterial complicated viral infection and be informed of the approach to the treatment of such conditions.

Defective bacterial clearance is responsible for the enhanced lung pathology characteristic of Mannheimia haemolytica pneumonia in bighorn sheep.

The molecular and cellular basis for the enhanced lung pathology and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear leukocytes (PMNs) of BHS are four- to eight-fold more susceptible to M. haemolytica leukotoxin-induced cytolysis, which is likely to reduce the number of functional phagocytes in the lung. We hypothesized that enhanced lung pathology is due to defective clearance of M. haemolytica from the lungs of BHS. To test this hypothesis, M. haemolytica (1 × 10(7) colony forming units [cfu]) were inoculated intra-tracheally into three groups each of BHS and DS, which were euthanized and necropsied at 4, 12, and 18 h post-inoculation (hpi). Bacterial and leukocyte counts were performed on broncho-alveolar lavage fluid (BALF) collected at necropsy. BALF from BHS euthanized at 4 and 12 hpi contained a significantly higher number of M. haemolytica than that from DS. More importantly, DS did not have any bacteria in BALF at 18 hpi, while the BHS still had significant numbers. As expected, the BHS did exhibit more extensive lung lesions at 12 and 18 hpi when compared to DS. At 18 hpi, necrotic PMNs were observed in the lesional lung tissues of BHS, but not DS. Furthermore, BALF from BHS had significantly lower titers of antibodies to Lkt and surface antigens of M. haemolytica, than that of DS. These findings suggest that the enhanced pathology in BHS lungs is due to defective clearance of M. haemolytica from the lungs.

Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap formation by bovine neutrophils.

Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktC mutant of M. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT or M. haemolytica cells. Further investigation revealed that NETs formed in response to M. haemolytica are capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing of M. haemolytica cells in bovine NETs. Understanding NET formation in response to M. haemolytica and its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease.

Mannheimia haemolytica serotype A1 exhibits differential pathogenicity in two related species, Ovis canadensis and Ovis aries.

Mannheimia haemolytica causes pneumonia in both bighorn sheep (BHS, Ovis canadensis) and domestic sheep (DS, Ovis aries). Under experimental conditions, co-pasturing of BHS and DS results in fatal pneumonia in BHS. It is conceivable that certain serotypes of M. haemolytica carried by DS are non-pathogenic to them, but lethal for BHS. M. haemolytica serotypes A1 and A2 are carried by DS in the nasopharynx. However, it is the serotype A2 that predominantly causes pneumonia in DS. The objectives of this study were to determine whether serotype A1 exhibits differential pathogenicity to BHS and DS, and to determine whether leukotoxin (Lkt) secreted by this organism is its primary virulence factor. Three groups each of BHS and DS were intra-tracheally administered either 1 x 10(9)cfu of serotype A1 wild-type (lktA-Wt group), Lkt-deletion mutant of serotype A1-(lktA-Mt group), or saline (control group), respectively. In the lktA-Wt groups, all four BHS died within 48h while none of the DS died during the 2-week study period. In the lktA-Mt groups, none of the BHS or DS died. In the control groups, one DS died due to an unrelated cause. Necropsy and histopathological findings revealed that death of BHS in the lktA-Wt group was due to bilateral, fibrinohemorrhagic pneumonia. Although the A1-Mt-inoculated BHS were clinically normal, on necropsy, lungs of two BHS showed varying degrees of mild chronic pneumonia. These results indicate that M. haemolytica serotype A1 is non-pathogenic to DS, but highly lethal to BHS, and that Lkt is the primary virulence factor of M. haemolytica.

Effect of vaccinating lambs against pneumonic pasteurellosis under New Zealand field conditions on their weight gain and pneumonic lung lesions at slaughter.

In a field trial, 9174 lambs from seven commercial sheep flocks with a history of subclinical pneumonia were either vaccinated with Ovipast Plus (Intervet) or given a placebo by systematic random allocation; they were vaccinated twice at an interval of four to six weeks and grazed on pasture in the same paddocks. They were weighed at the first vaccination, 11 and 23 weeks later, and one to three days before they were slaughtered. The extent of the pneumonic lesions in their lungs was scored visually postmortem. A subset of pneumonic lung samples was examined bacteriologically and histopathologically. There were no statistically significant differences between the pneumonic lesions at slaughter or the mean average daily weight gains of the vaccinated and placebo-treated lambs between 11 and 23 weeks or between first vaccination and slaughter. The vaccinated lambs had a lower mean daily gain between first vaccination and 11 weeks. The extent of pneumonic lesions at slaughter was negatively correlated with the mean daily gain between first vaccination and slaughter. There were no significant differences between the frequency of isolation of Mannheimia (Pasteurella) haemolytica and Pasteurella trehalosi or the histopathological classification of disease between pneumonic lung samples from the placebo-treated and vaccinated lambs.

Use of computed tomography to evaluate pathologic changes in the lungs of calves with experimentally induced respiratory tract disease.

OBJECTIVE: To optimize methods for the use of computed tomography (CT) to assess pathologic changes in the lungs of calves and to determine the effect of treatment on lung consolidation. ANIMALS: 10 male Holstein calves. PROCEDURES: Calves were anesthetized to facilitate CT imaging of the thorax. After initial images were obtained, pneumonia was induced in the calves by inoculation through a bronchoscope. Two calves were used in a preliminary study to refine the inoculation dose and optimize CT images. Four calves were administered florfenicol and 4 calves were untreated control animals. Serial images were obtained 24, 48, and 72 hours after inoculation. After final images were obtained, calves were euthanized, and lung consolidation was estimated by use of lung surface area scoring and water displacement. These estimates were compared with estimated lung consolidation obtained by use of CT. RESULTS: Calves had rapid disease progression. Percentage of lung consolidation was not significantly different between treatment groups for any of the estimation methods. Results of an ANOVA of the 3 assessment methods indicated significant differences among methods. Estimates of the percentage of lung consolidation obtained by use of surface area scoring and CT correlated well, whereas water displacement estimates correlated poorly with other methods of consolidation estimation. CONCLUSIONS AND CLINICAL RELEVANCE: Because of the correlation with other methods for estimation of lung consolidation, CT has the potential to be used to monitor disease progression in calves with experimentally induced respiratory tract disease.

Meta-analysis of treatment of cattle with bovine respiratory disease with tulathromycin.

The objective of this study was to evaluate the comparative efficacy of tulathromycin at resolving bovine respiratory disease in North American feedlot cattle. This study was a systematic review of published literature. A search was conducted to identify all manuscripts relating to antibiotic treatment of cattle with respiratory disease. Relevant studies reported treatment with tulathromycin of naturally occurring respiratory disease in beef cattle in North America. Studies which failed to use randomization to minimize bias were excluded from the review. The relative risk of retreatment for bovine respiratory disease was calculated for each study included in the final review. Initially, 782 potential manuscripts were identified. After relevance screening and quality assessment, 21 high quality manuscripts were available for analysis. Two peer reviewed publications and two technical reports describing 14 trials compared tulathramycin with tilmicosin or florfenicol. In the meta-analysis of studies comparing tilmicosin with tulathromycin, the summary Mantel-Haenszel relative risk was 0.51 (95% confidence interval 0.45-0.57). It was not possible to calculate a summary Mantel-Haenszel relative risk comparing florfenicol with tulathromycin as the only three studies reported this comparison. When using a meta-analysis to combined data from randomized clinical trials reporting treatment with tulathromycin or either florfenicol or tilmicosin, tulathromycin was associated with an approximately 50% reduction in the risk of re-treatment for bovine respiratory disease compared with treatment with tilmicosin.

An aetiopathological study of chronic bronchopneumonia in lambs in Ireland.

Chronic bronchopneumonia in lambs, also known as 'atypical' or 'chronic, non-progressive' pneumonia is a common, frequently sub-clinical disease affecting animals under 12-months-old in intensive production systems. Infection with both Mycoplasma ovipneumoniae and Mannheimia haemolytica have been implicated in the aetiology of this condition and a variety of pulmonary lesions can result. In this study, detailed laboratory examination of 30 abattoir-derived lungs with the characteristic gross features of atypical pneumonia (AP) was carried out with a view to refining and correlating the histopathological and microbiological criteria required for the diagnosis of this disease. For the first time a broad range of laboratory detection techniques including bacterial and virus isolation, fluorescent antibody tests and immunohistochemistry were used in parallel to identify potential causative pathogens such as M. ovipneumoniae, M. haemolytica, parainfluenza type-3 (PI3) virus and respiratory syncytial virus (RSV) in AP lesions. The most consistent finding was the association of gross AP lesions with M. ovipneumoniae, identified by either culture or immunohistochemistry in 27 (90%) of the 30 cases. However the presence M. ovipneumoniae organisms or antigen did not consistently correlate with particular histopathological changes. Furthermore, peri-airway lymphoid hyperplasia, intra-alveolar exudation and nodular 'hyaline scars', which are all previously reported microscopic lesions of AP, were not identified in 12 (40%) of the cases and isolation of M. haemolytica was over-represented in lungs exhibiting suppurative lesions. These findings illustrate the complex aetiopathogenesis of this disease and highlight the requirement to use a combination of diagnostic criteria in its laboratory diagnosis.

Therapeutic efficacy of tulathromycin, a novel triamilide antimicrobial, against bovine respiratory disease in feeder calves.

Efficacy and field safety of tulathromycin administered as a single-dose treatment to crossbreed beef calves with undifferentiated bovine respiratory disease (BRD) were evaluated in a multicenter field study conducted at four US feedlots. Two hundred castrated male calves were enrolled at each study site. The treatment groups were physiologic saline (n = 160) given SC at 0.02 ml/kg, tulathromycin (n = 320) given SC at 2.5 mg/kg, and tilmicosin (n = 320) given SC at 10 mg/kg. Nasopharyngeal swabs for bacterial culture were obtained before treatment. The cure rate for calves treated with tulathromycin (78%) and tilmicosin (65%) was significantly (P < or = .0001) higher than that of calves treated with saline (23.8%). The cure rate of calves treated with tulathromycin (78.4%) was significantly (P = .0007) higher than that of calves treated with tilmicosin (64.9%). No adverse events related to tulathromycin were reported. Under the conditions of this study, tulathromycin administered as a single-dose treatment was efficacious in the treatment of undifferentiated BRD.

Efficacy of tulathromycin compared with tilmicosin and florfenicol for the control of respiratory disease in cattle at high risk of developing bovine respiratory disease.

Three studies conducted at feedlots in Colorado, Idaho, and Texas examined the comparative efficacy of tulathromycin injectable solution for the treatment of cattle at high risk of developing undifferentiated bovine respiratory disease (BRD). Each study randomly allocated 250 calves to receive tulathromycin at 2.5 mg/kg and 250 calves to receive either tilmicosin at 10 mg/kg (Colorado site) or florfenicol at 40 mg/kg (Idaho and Texas sites) on arrival at the feedlot. Calves were housed by treatment group in pens with 50 calves/pen. Beginning 3 days after antimicrobial treatment, cattle were observed for signs of BRD daily until harvest. In all three studies, the treatment success rates at 28 days after treatment and at harvest were significantly higher (P < or = .013) for cattle treated with tulathromycin than for cattle treated with either tilmicosin or florfenicol. Fewer tulathromycin-treated cattle were removed from the group as "chronics" or "mortalities" at 28 days posttreatment (P < or = .014) in all three studies. Tulathromycin demonstrated superior efficacy compared with tilmicosin and florfenicol when treating groups of high-risk cattle before the onset of signs of BRD.

Comparative efficacy of tulathromycin, tilmicosin, and florfenicol in the treatment of bovine respiratory disease in stocker cattle.

The therapeutic efficacy and field safety of tulathromycin were evaluated in stocker calves with undifferentiated bovine respiratory disease (BRD) in three field studies conducted over two consecutive grazing seasons in Nebraska. Eight hundred calves exhibiting clinical signs of BRD and with rectal temperatures of 104 degrees F or higher were treated with tulathromycin (n = 340), florfenicol (n = 240), or tilmicosin (n = 220) and evaluated for approximately 60 days. Florfenicol and tilmicosin were administered as single SC injections according to labeled dosage. Tulathromycin was administered as a single SC injection of 2.5 mg/kg. In all three studies, the cure rate of calves 60 days after treatment with tulathromycin was significantly higher (P < or = .05) than that of calves treated with florfenicol or tilmicosin. Suspected adverse reactions were not reported for any of the study drugs. Tulathromycin proved to be significantly more effective than either florfenicol or tilmicosin in the treatment of BRD in stocker calves.

Comparative efficacy of tulathromycin versus florfenicol and tilmicosin against undifferentiated bovine respiratory disease in feedlot cattle.

Four studies conducted at feedlots in Greeley and Wellington, Colorado; Nebraska; and Texas compared the efficacy of tulathromycin to florfenicol or tilmicosin for the treatment of cattle with undifferentiated bovine respiratory disease (BRD) and subsequent feedlot performance and carcass characteristics. In each study, 100 calves with BRD were treated with tulathromycin given SC at 2.5 mg/kg body weight. At the Greeley, CO, and Nebraska study locations, 100 calves were treated with florfenicol given SC at 40 mg/kg body weight, and at the Wellington, CO, and Texas study locations, tilmicosin was given SC at 10 mg/kg body weight. Cure rate, a derived variable that included assessments of mortality, rectal temperature, and attitude and respiratory scores from day 3 to day 28 and day 3 through harvest, was the primary assessment of BRD efficacy. Cure rates of calves treated with tulathromycin were significantly (P < or = .009) higher than those calves treated with florfenicol. At Wellington, CO, the cure rate of calves treated with tulathromycin was significantly higher (P < or = .018) compared with tilmicosin-treated calves. The differences in cure rates between tulathromycin and tilmicosin treatment groups in the Texas study were not significantly different (P > .05). Tulathromycin was more efficacious in the treatment of undifferentiated BRD compared with florfenicol and, in one study, compared with tilmicosin.

Evaluation of the therapeutic activity of tulathromycin against swine respiratory disease on farms in Europe.

The clinical efficacy of tulathromycin in the treatment of natural outbreaks of swine respiratory disease (SRD) was evaluated at five European sites. Pigs (1 to 6 months of age) exhibiting clinical signs of SRD were treated intramuscularly with tulathromycin (n = 247) at 2.5 mg/kg on day 0 versus either tiamulin (n = 102) at 15 mg/kg on days 0, 1, and 2 (Germany, the Netherlands, and the United Kingdom) or florfenicol (n = 20) at 15 mg/kg on days 0 and 2 (France). Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae infections were the most frequently diagnosed pathogens. For both tulathromycin-treated animals and those treated with tiamulin or florfenicol, there were significant (P = .0001) reductions in mean rectal temperature and the severity of abnormal clinical signs on days 2 and 10 compared with day 0. There were no significant differences (P > .05) between treatments in average daily weight gain. Tulathromycin was found to be safe and highly effective in the treatment of natural outbreaks of SRD.