Association between lung consolidation and serum amyloid-A and haptoglobin, and the potential of acute phase proteins to differentiate primary respiratory tract pathogens in calves

Abstract

Bovine respiratory disease (BRD) remains a leading cause of economic losses, hampered animal welfare and antimicrobial use. The use of acute phase proteins (APPs), such as serum amyloid A (SAA) and haptoglobin (Hp), has been explored for the detection of BRD, as defined by clinical signs. However, whether these APPs are also associated with lung consolidation, as determined by thoracic ultrasonography, and have the potential to differentiate causative pathogens is unknown. Therefore, the primary objective of this study was to explore the association between lung consolidation and SAA and Hp. The second objective was to determine the ability of both SAA and Hp to differentiate pathogen groups (Mycoplasmopsis bovis, viruses and Pasteurellaceae). A cross-sectional study including 170 calves from 25 different herds with a history of Mycoplasmopsis bovis (M. bovis) (endemic, n = 94, 9 herds) or herds (including M. bovis positive herds) that met the inclusion criteria of an outbreak of BRD (i.e., the presence of one or more clinical signs associated with BRD, affecting multiple animals (5 animals; 15% ill animals in the same airspace on a farm within a 48-h period) (epidemic, n = 76, 16 herds) was conducted between 2020 and 2022 in Belgium. Clinical examination, quick thoracic ultrasonography (qTUS), blood sampling and non-endoscopic bronchoalveolar lavage (nBAL) were performed on each calf. Linear mixed effect models with a random intercept for herd were fitted, to determine the association between lung consolidations (depth ≥ 1 cm or ≥3cm) or clinical BRD (UC Davis BRD scorecard positive) and serum SAA and Hp concentrations. Furthermore, multivariable models (linear mixed effect models) were used to evaluate the mutually adjusted associations between pathogen groups and APP concentrations. Test characteristics of APP concentrations to predict the presence of lung consolidation or pathogen groups were assessed, and potential SAA and Hp cutoffs, determined by Youden index, were evaluated. Lung consolidation (≥1 cm) was positively association with higher Hp concentrations in epidemic conditions [regression coefficient (β): 5.3 (95% confidence interval (CI): 1.4-20.3)], while more severe lung consolidation (≥3 cm) was associated with higher Hp concentrations in endemic conditions [β: 3.6 (95% CI: 1.2-11.0)]. No positive association was found between lung consolidation and SAA. Yet, a positive association between M. bovis and SAA was observed [β: 2.3 (95% CI: 1.3-4.3)]. At last, no association was found between M. Bovis and Hp. For Hp, the best cutoff to predict a lung consolidation (≥1 cm) was 2.33 µg/mL (Se: 81.8% and Sp: 66.7%). Moreover, to detect M. bovis among calves with a lung consolidation (≥1 cm), a SAA cutoff of 174.84 µg/mL was determined (Se: 77.8% and Sp: 87.5%). Despite the observed relationships between lung consolidation, pathogen groups, and APPs, the test characteristics in this study suggest that Hp and SAA are currently limited in their (practical) use for the detection of lung consolidation or M. bovis.