RaDiCal: Rapid diagnosis of Calf Pneumonia

Lead Research Organisation: University of Surrey
Department Name: Veterinary Medicine & Science

Abstract

We shall develop a rapid, sensitive, cost-effective on-farm diagnostic test capable of detecting the organisms responsible for calf pneumonia to inform herd management and reduce the unnecessary use of antibiotics. Early diagnosis of pneumonia will allow the farmer to administer treatment in a proportionate and timely way.

Calf pneumonia is a complex disease caused by a variety of infectious agents. Typically, the clinical disease is caused by certain species of bacteria that may normally cause no adverse effects to the lungs but do so when the animal is compromised in some way, such as a specific viral infection in combination with other stress factors, such as weaning, changes of feed, variation in ambient temperature and humidity. The estimated lifetime economic cost of a case of pneumonia in a dairy heifer is £772, highlighting the potential returns from investing in reducing the impact of this disease. Despite the substantial cost that calf pneumonia causes the UK cattle industry, most farmers prefer to reduce the likelihood of the disease occurring or rely on detecting pneumonia through non-specific means. That is not to say that diagnostic tests are not available, but the high cost of tests and the fact that the results are delayed and therefore cannot inform treatment decisions are likely reasons why these are not used routinely. We intend to understand the impediments to livestock diagnostic test use in more detail in this project through engagement with farmers, vets, and calf rearers.

Recent developments in rapid molecular diagnostics (many by the project team) offer the possibility of delivering a test that is considerably cheaper, quicker and more sensitive than existing commercial tests, opening up the opportunity to use such a test for routine surveillance on-farm. This would enable early intervention and the development of specific treatment protocols, thus reducing antimicrobial resistance and improving calf welfare. Our project sits at the intersections between policy change, economic opportunity, changing practice, public perception of the industry, and even antibiotic stewardship.

We are a new and focused partnership that combines working knowledge of dairy farming, expertise in veterinary infectious disease, diagnostic test development and stakeholder engagement methods. The test will be based on simultaneous detection of any of the six most common infections associated with calf pneumonia using a simple swab of the nasal passages, not unlike the current lateral flow tests for COVID-19. The swab will be placed in a novel device developed by the project partners that gives a simple final readout of the test result using a lateral flow device. Proof of principle has been demonstrated for the technology we intend to adopt for the detection of at least some of the pathogens associated with calf pneumonia, and three of the partners have experience of the development of rapid tests using this technology for pathogens of veterinary importance, and respiratory infectious disease testing in humans (incl. COVID-19).

However, developing a test is only half the story, and we must ensure the test is co-developed with those who will ultimately use it. One of the partners is a dairy farmer, another a livestock veterinarian, and two others have worked with calf rearers for the last five years on pneumonia management and antibiotic resistance. Using methods, such as interviews/workshops with calf rearers and vets, we shall ask questions such as, how do you currently control pneumonia, how quick does the test need to be from start to result, how much should it cost, which sales channel is most attractive, and what will you do differently in response to the test result? This will be vital information to ensure the test we develop has the best chance of being used on farm to the benefit of animal health and welfare, the GB cattle industry, and beyond.

Technical Summary

We shall develop a rapid, sensitive, cost-effective on-farm test to diagnose pneumonia, to 1) inform herd management; 2) mitigate the economic cost caused by the long-term of damage of pneumonia on productivity; and 3) reduce the unnecessary use of antibiotics through better, evidence-based prescribing.

Calf pneumonia is a 'disease complex', caused by co-infection with a variety of pathogens, together with other environmental/stress factors, such as weaning, variation in temperature and humidity. The estimated lifetime economic cost of a case of pneumonia in a dairy heifer is £772, highlighting the potential returns from investing in reducing the impact of this disease. Despite the substantial cost that calf pneumonia causes the UK cattle industry, most farmers prefer to reduce the likelihood of the disease occurring or rely on detecting pneumonia through non-specific means. That is not to say that specific diagnostic tests are not available, but there are reasons why farmers are not using them routinely. We intend to understand the impediments to diagnostic test use in more detail through engagement with farmers and calf rearers.

Recent developments in rapid molecular diagnostics, including loop-mediated isothermal amplification (LAMP), have opened the possibility of rapid, on-farm diagnosis of calf pneumonia using nasal swabs. Drawing on the complementary skills of our new partnership, the test will be co-developed through stakeholder engagement in a virtuous circle and technically, will combine novel sample preparation/DNA extraction in a disposable cartridge with readout on a lateral flow device (LFD) with preliminary validation data, and be the first to combine simultaneous detection of bacteria and DNA viruses from clinical samples to aid diagnosis. Coupling the LFD readout to smartphone AI-based, on-farm decision support will allow for early intervention and the application of specific, better informed treatment protocols.
 
Description Member of RUMA SA & E
Geographic Reach National 
Policy Influence Type Contribution to new or improved professional practice
Impact Improved antimicrobial stewardship.
 
Description UKRI-BBSRC Bioscience for an Integrated Understanding of Health Strategy Advisory Panel
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
 
Title LAMP test for bovine respiratory disease pathogens 
Description Primers suitable for development of a multiplex LAMP test for bovine respiratory disease were identified and proof of concept demonstrated with cattle nasal swabs spiked with nucleic acid from the pathogens. 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact Proof of concept is sufficiently encouraging and the market desire and opportunity there to develop this test to a higher technology readiness level through the BBSRC follow-on Fund and commercial engagement. 
 
Title LAMP test for bovine respiratory disease pathogens 
Description Proof of concept is sufficiently encouraging and the market desire and opportunity there to develop this test to a higher technology readiness level through the BBSRC follow-on Fund and commercial engagement. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2023
Development Status Actively seeking support
Impact Engagement with a company potentially interested in partnering with us for further development, as well as continued academic collaboration between the University of Surrey and University of Glasgow. 
 
Description Endemic Livestock Disease Initiative Update Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The PI was invited to present the outcomes of the project at The Endemic Livestock Disease Initiative Update Event, hosted by NFU Stoneleigh, Warwickshire on 27th October 2023. It was an opportunity for researchers and industry bodies to get together and celebrate the achievements and impacts of the Phase 1 Catalysing projects. The event attracted 42 attendees including researchers from the Catalysing, Priming and Phase 2 Endemic Livestock Disease Initiative community and industry bodies including DEFRA, NFU, AHDB, BCVA, PVS and BVA.
Year(s) Of Engagement Activity 2023
 
Description Expert Co-Design Focus Group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A conclusion from the previous stakeholder workshop is that we should undertake further stakeholder engagement to produce a draft protocol for use of the test as part of a management plan for calf pneumonia. We did this through an online Expert Co-Design Focus Group. The aim of this workshop was to design a protocol/standard operating procedure for the use of a test that identifies and monitors respiratory pathogens in cattle. The workshop was held as an online event held using Microsoft Teams. A range of stakeholders participated in the workshop from academic, commercial and practice backgrounds. In focusing on the purpose of the workshop, all participants were present at all times and break out rooms were not used. Discussion was mainly through participants talking with some use of the chat function. All participants were able to contribute to the discussion in the workshop. In order to ensure engagement, the participants were responsible for setting the agenda of the workshop, especially the practicing vet participants.
Year(s) Of Engagement Activity 2023
 
Description Interactive Stakeholder Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact An interactive stakeholder workshop entitled, 'Calf Pneumonia - Addressing the challenge together' was held at Regilbury Park dairy Farm near Bristol on 27 April. The entire project team attended except for Abi Reader. A total of 45 individuals were invited to the meeting, seeking representation from farming, the veterinary profession, industry/pharma, government, and welfare organisations. Sixteen delegates attended. Dr Tim Potter from Westpoint Farm Vets discussed the challenges the farming industry face in managing the disease during calving, feeding, and weaning. In addition to a tour of the farm and discussion of the problems in context, we presented our progress towards the development of a rapid diagnostic test for pneumonia. Attendees had the opportunity to evaluate the test prototype and provide valuable feedback regarding the test's design and operation for us to use in further product design and development. The event was free to attend.
Year(s) Of Engagement Activity 2023
 
Description UKRI-BBSRC Bioscience for an Integrated Understanding of Health Strategy Advisory Panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact The Bioscience for an Integrated Understanding of Health Strategy Advisory panel is concerned with improving the health and wellbeing of both animals and humans across the life-course, with a particular emphasis on generating a deep, integrated understanding of the 'healthy system', and of the factors that maintain health and wellness under stress and biological or environmental challenge. The PI was invited to present on the topic Diagnostics Platform Technologies and contributed to discussion and debate in the session focussed on a One Health Approach to Infectious Diseases and AMR.
Year(s) Of Engagement Activity 2023