P.PSH.0874 - Improving bovine respiratory disease control through the characterisation of pathogen-host interactions

Summary

The research described in this report was conducted to improve the management and prevention of bovine respiratory disease (BRD) in Australian feedlot cattle. The research is targeted to the Australian feedlot sector where BRD is the most important cause of cattle morbidity and mortality. BRD costs the sector between $60–100M annually in lost productivity and as a result, research is required to improve the prevention and management of this disease.

Objectives

The objectives of this project were to provide tools for the improved management of BRD in feedlot cattle, delivered via a multifaceted approach based on an understanding of host-pathogen interactions, including:

• development of new diagnostic assays for pathogens in the bovine respiratory disease complex
• characterisation of the DNA and RNA viromes present in the tissues of cattle that have died of BRD to inform the development of novel vaccines to protect animals from BRD
• identification of putative biomarkers for clinically healthy animals with respect to BRD, to contribute to improving the diagnosis of the disease
• identification of potential biomarkers in the blood of cattle infected with bovine herpesvirus 1 and bovine viral diarrhoea virus 1, two viruses frequently associated with BRD in Australia. These biomarkers will improve the diagnosis of BRD cases and underpin treatment decisions.

Key findings

This study has identified two potential biomarkers of infection for two of the viruses which are strongly associated with BRD development in Australian feedlot cattle.

The DNA/RNA virome present in tissues collected from cases of BRD in Australian feedlot cattle was characterised. Consistent with published studies, there is a wider variety of viruses present in these tissues than the four or five viruses historically associated with BRD.

The genome wide analyses determine an estimate for the heritability of BRD resistance of 0.20 ± 0.04, this supports further investigations to improve this estimate.

Within the sampled populations, unexpected high viral loads of bovine herpesvirus 1 were detected in vaccinated cattle. Oxford Nanopore Technologies (ONT) sequencing proved to be highly amenable to detecting a wide range of bacteria in nasal swabs collected from cattle being treated for BRD. The application of strategies to remove bovine DNA from samples prior to analyses is essential.

Oxford Nanopore Technologies (ONT) sequencing enabled the detection of antimicrobial resistance genes in nasal swabs of cattle being treated for BRD.

Benefits to industry

The results of this project have the potential to improve the identification and management of cattle affected by BRD, the most important cause of morbidity and mortality in Australian feedlot cattle. Putative biomarkers for BRD were identified and with further development these could be used to identify BRD affected cattle. The capacity to objectively identify cattle with BRD will underpin decisions to treat affected animals and enhance antimicrobial stewardship.

A robust estimated breeding value has been determined for BRD resistance. The inclusion of this estimate in breeding plans would enable the selection of cattle that are less likely to be affected by BRD during their time on feedlots.

New approaches have been developed to enable the detection of bacteria and AMR genes in cattle being treated for BRD. The molecular assays developed to detected AMR genes have the capacity to improve antimicrobial stewardship by enabling the detection and monitoring of antimicrobial resistance in feedlot cattle.

MLA action

MLA will continue research and development focused on prevention of bovine respiratory disease in feedlots.

Future research

Further research is recommended to better understand the detection of bovine herpesvirus 1 in cattle being treated for BRD. Not only was the rate of detection higher than might be expected, the time of treatment for some of these animals was well outside the window of high BRD risk. Similarly, the viral loads of some animals were extraordinarily high and clearly warrant further investigation.

Further research is also required to increase the number of animals included in the BRD genetic resistance estimates. Identifying sources of already genotyped cattle that move through the feedlot system would be a cost-effective way to achieve this.

The results of this study also support the further development of the ONT sequencing to support the feedlot sector in antimicrobial resistance monitoring. The experimental approaches utilised in this project suggest this is a highly feasible approach. However, it is likely that additional improvements in the technology, specifically the underpinning bioinformatics required before it can be deployed throughout the sector without expert assistance.