The effect of aerosolized bacterial lysate on experimentally induced Mannheimia haemolytica pneumonia in calves.

Bovine respiratory disease (BRD) often occurs during specific periods of increased susceptibility when stress, viral infection, or reduced air quality are thought to suppress respiratory defences. The innate immune system is rapidly responsive and broadly protective and could be a target for preventing BRD during these periods of increased susceptibility. This study tested the hypothesis that stimulation of pulmonary innate immune responses by aerosol delivery of a lysate of killed Escherichia coli and Staphylococcus aureus bacteria would protect calves against Mannheimia haemolytica pneumonia. Ten clean-catch colostrum-deprived Holstein calves were randomly assigned to receive either aerosolized bacterial lysate or saline 24 hours before M. haemolytica challenge. Effects of this treatment on clinical, hematologic, microbiologic, and pathologic outcomes were assessed. Compared to controls, lysate-treated calves had lower serum haptoglobin and blood leukocyte and neutrophil concentrations following M. haemolytica challenge. There were no differences in temperature, heart and respiratory rates, clinical scores, ultrasound lesions, or number of M. haemolytica in the nasal cavity or lung. Thus, treatment with bacterial lysate prior to M. haemolytica challenge appeared to ameliorate early measures of inflammation but did not provide sufficient protection to substantially alter the course of disease.

La maladie respiratoire bovine (BRD) survient souvent pendant des périodes spécifiques de sensibilité accrue lorsque le stress, une infection virale ou une qualité de l'air réduite sont censés supprimer les défenses respiratoires. Le système immunitaire inné est rapidement réactif et largement protecteur et pourrait être une cible pour prévenir la BRD pendant ces périodes de sensibilité accrue. Cette étude a testé l'hypothèse selon laquelle la stimulation des réponses immunitaires innées pulmonaires par la délivrance d'aérosols d'un lysat de bactéries Escherichia coli et Staphylococcus aureus tuées protégerait les veaux contre la pneumonie à Mannheimia haemolytica. Dix veaux Holstein dont on a limité la contamination bactérienne et privés de colostrum ont été répartis au hasard pour recevoir soit un lysat bactérien en aérosol, soit une solution saline 24 heures avant une infection défi par M. haemolytica. Les effets de ce traitement sur les résultats cliniques, hématologiques, microbiologiques et pathologiques ont été évalués. Comparativement aux témoins, les veaux traités au lysat présentaient des concentrations sériques d'haptoglobine et de leucocytes et de neutrophiles sanguins plus faibles après la provocation par M. haemolytica. Il n'y avait aucune différence dans la température, les fréquences cardiaques et respiratoires, les scores cliniques, les lésions échographiques ou le nombre de M. haemolytica dans la cavité nasale ou les poumons. Ainsi, le traitement avec un lysat bactérien avant la provocation par M. haemolytica a semblé améliorer les réactions précoces de l'inflammation mais n'a pas fourni une protection suffisante pour modifier substantiellement l'évolution de la maladie.(Traduit par Docteur Serge Messier).

Effect of aerosolized bacterial lysate on development of naturally occurring respiratory disease in beef calves.

BACKGROUND: Bovine respiratory disease (BRD) is a major problem affecting beef cattle after arrival to feedlots. Alternatives to antibiotics are needed for prevention. HYPOTHESIS: Stimulation of pulmonary innate immune responses at the time of arrival to a feedlot reduces the occurrence and severity of BRD. ANIMALS: Sixty beef steers at high risk of BRD. METHODS: Randomized, double-blinded, placebo-controlled study. Calves received saline or a lysate of Staphylococcus aureus and Escherichia coli by aerosol, at 16 hours after feedlot arrival. Calves were monitored for 28 days for disease outcomes and levels of Mycoplasma bovis and Mannheimia haemolytica in nasal swabs. RESULTS: Death from M bovis pneumonia was significantly greater in lysate-treated animals (6/29, 24%) compared to controls (1/29, 3%; odds ratio = 10.2; 95% confidence interval [CI] = 1.1-96.0; P = .04). By 28 days after arrival, 29/29 lysate-treated calves had ultrasonographic pulmonary consolidation compared to 24/29 control calves (P = .05). Lysate-treated calves had lower weight gain compared to control calves (-8.8 kg, 95% CI = -17.1 to -0.5; P = .04), and higher body temperatures on days 4, 7, and 21 (0.19°C; 95% CI = 0.01-0.37; P = .04). Nasal M bovis numbers increased over time and were higher in lysate-treated calves (0.76 log CFU, 95% CI = 0.3-1.2; P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Aerosol administration of a bacterial lysate exacerbated BRD in healthy high-risk beef calves, suggesting that respiratory tract inflammation adversely affects how calves respond to subsequent natural infection with M bovis and other respiratory pathogens.

Development of an aerosolized Mannheimia haemolytica experimental pneumonia model in clean-catch colostrum-deprived calves.

Mannheimia haemolytica is an important cause of bovine respiratory disease (BRD). BRD is usually a multifactorial disease with host factors and viral infections influencing pathogenesis. Previous studies that have attempted to experimentally induce pneumonia using aerosolized M. haemolytica alone have produced inconsistent results, yet an aerosol model would be useful to study the details of early infection and to investigate the role of innate defences in pathogenesis. The objective of these studies was to develop and characterize an aerosolized M. haemolytica disease model. In an initial study, conventionally raised calves with higher levels of antibody against M. haemolytica leukotoxin developed acute respiratory distress and diffuse alveolar damage, but did not develop bronchopneumonia, following challenge with M. haemolytica serotype 1. Clean-catch colostrum-deprived calves challenged with 1 × 1010 colony forming units of M. haemolytica serotype 1 consistently developed bronchopneumonia, with elevations in rectal temperature, serum haptoglobin, plasma fibrinogen, and blood neutrophils. Mannheimia haemolytica serotype 1 was consistently isolated from the nasal cavities and lungs of challenged calves. Despite distribution of aerosol and isolation of M. haemolytica in all lung lobes, gross lesions were mainly observed in the cranioventral area of lung. Gross and histologic lesions included neutrophilic bronchopneumonia and fibrinous pleuritis, with oat cells (necrotic neutrophils with streaming nuclei), and areas of coagulative necrosis, which are similar to lesions in naturally occurring BRD. Thus, challenge with M. haemolytica serotype 1 and use of clean-catch colostrum-deprived calves with low or absent antibody titres allowed development of an effective aerosol challenge model that induced typical clinical disease and lesions.