Large animal lung studies highlight One Health research

Researchers are using novel methods to understand and tackle a virus that spreads undetected among sheep flocks, with fatal outcomes.  

The Jaagsiekte sheep retrovirus (JSRV), spread by airborne transmission, poses a significant and ongoing threat to animal welfare, flock productivity and the economic sustainability of the sheep industry.  

The infectious virus leads to a cancer in the lungs of sheep called Ovine Pulmonary Adenocarcinoma (OPA), which bears similarities to human lung cancers.  

Insights gained from studies at the Roslin Institute, Royal (Dick) School of Veterinary Studies and the Moredun Research Institute may help mitigate serious livestock losses, as well as enabling improved understanding of human lung cancer.  

Pivotal experiments conducted over 80 years ago demonstrated the infectious nature of OPA. Despite the multitude of scientific advancements since then, we still do not understand how infectious an individual sheep is in relation to tumour size, with the control of OPA remaining a significant challenge.  

Diagnosis is difficult, as disease can be undetectable in the early stages. The virus does not lead to production of antibodies, ruling out blood tests as a means of detection.  

There is no vaccine or treatment for JSRV, and sheep affected by OPA are culled. Preventative steps typically include maintaining a closed flock of disease-free animals, quarantining new animals, and ensuring good practice to prevent infection entering or leaving farms. 

To better understand the virus and associated disease, researchers are gaining valuable insights through the development of a novel sheep model.  

Understanding OPA in sheep offers an opportunity to improve livestock health and welfare, and prevent losses. It can also shed light on human lung cancer.  

Studies using the state-of-the-art infrastructure at the Roslin Institute's Large Animal Research and Imaging Facility (LARIF) have shown that the development of OPA in sheep can be accurately tracked with both ultrasound and computed tomography (CT).  

Lung ultrasound offers the potential of identifying OPA lesions, with the procedure used in the screening of large commercial flocks.  

Dr Mark Gray, Senior Lecturer in Large Animal Research Surgery and Academic Lead of the LARIF, and his group, in association with Dr Chris Cousens and Dr David Griffiths at the Moredun Research Institute, are further investigating the use of ultrasound to diagnose OPA disease before large lung tumours develop, thereby enabling earlier OPA detection and better control of the disease.  

CT imaging provides the current standard for mapping lung cancer pathology. When combined with radiomic feature analysis, which extracts a large number of features from medical images that are not visible to the human eye, the potential exists to improve clinical decision-making.  

Other work by Dr Gray’s team demonstrates the potential use of radiomic analysis of sheep lung CT images for the early detection and management of OPA lung tumours.  

Worldwide, human lung cancer is the most frequently diagnosed cancer, with approximately 2.5 million new cases and 1.8 million cancer-related deaths occurring each year.  

Historically, mice have typically been used to investigate disease mechanisms and new cancer treatments. Unfortunately, these study models are poor predictors of clinical outcome, and seldom mimic the advanced stages of disease as experienced by people.  

Sheep have long been recognised as a valuable model for studying various human lung diseases due to their similar size, in addition to the anatomical and physiological similarities to the human respiratory system.  

OPA exhibits several key similarities to specific subtypes of human lung cancer, so much so that it is now regarded as a robust, relevant model for studying human lung cancer. In an effort to lessen the toxicities associated with many current lung cancer therapies, further work by Dr Gray’s group has involved the assessment of novel intratumoural drug delivery techniques using the OPA model.  

Developments in disease detection may be aided by artificial intelligence (AI), which could have a role to play in reducing noise and aiding accuracy, enabling the diagnosis of OPA before large tumours develop. Researchers are seeking to develop tests that can be deployed in flocks at scale. “A pen-side AI-enhanced diagnostic would offer a convenient, efficient way to screen flocks,” explains Dr Gray.  

“Questions also remain over when sheep can transmit disease,” continues Dr Gray. Preliminary data show variability in JSRV shedding in exhaled breath among sheep; while some sheep with large tumours secrete high levels of virus, others with similar tumour burdens show no detectable virus, suggesting the existence of high and low transmission risk animals.  

Dr Gray goes on to explain: “Diagnostics or environmental monitoring could be targeted to look for virus in sheep breath, or even in the air.” 

Further development will aid the design of rapid, non-invasive diagnostics for the benefit of livestock, while also offering valuable insights into detecting, diagnosing and treating lung diseases in humans.