Pioneering Vet Med research shields dairy cows from debilitating and untreatable disease

Researchers at the University of Calgary Faculty of Veterinary Medicine have made a significant breakthrough in the field of microbiology and phage therapy to treat a difficult-to-detect, debilitating, and untreatable and fatal disease in dairy cows. 

Johne’s disease (paratuberculosis) affects ruminants like cattle, sheep, and goats. It is a mycobacterial infection caused by the Mycobacterium avium subsp. paratuberculosis (MAP) pathogen. Young calves are the most likely to contract the disease, yet symptoms can take two to six years to manifest, during which the cow is unwittingly shedding the pathogen. 

Spread through fecal-oral transmission from mother to calf, or contaminated environments such as bedding or feed, partnered with a lengthy asymptomatic but still contagious stage, it’s reported to affect upwards of 50 per cent of dairy herds. With no treatment and limited preventive strategies, this is truly a disease to be reckoned with.

In a research article published in the Proceedings of the National Academy of Sciences (PNAS) researchers have showcased the efficacy of a novel bacteriophage preventive cocktail in almost entirely protecting against Johne’s disease before it is contracted. Phage therapy uses viruses called bacteriophages to target and kill specific harmful bacteria, providing an alternative to antibiotics for treating infections. 

The novelty of this therapy is its use as a preventive measure, in which these viruses are applied before an infection occurs to protect against bacterial diseases. 

Remarkably, the researchers found that the bacteriophages remained in the calves' intestines for several weeks. These phages stay in the intestinal wall, ready to attack MAP bacteria before they can infect the tissues. The researchers believe this long-lasting presence could be crucial for protecting dairy calves over the long term.

“Think of this preventive phage therapy as a daily yogurt of precisely targeting biological nano-machines in the form of phages," says lead researcher Dr. Jeroen De Buck, professor in veterinary microbiology and research chair in Bacterial Diseases of Dairy Cattle. “Our research lays the foundations for phage therapy as a solution for combating MAP infections."

This breakthrough has implications beyond Johne’s disease as well.

De Buck says, "Increasing antibiotic resistance issues have put phage therapy in the spotlight in animal and human medicine. Our study brings a new perspective to this field by demonstrating, for the first time, the potential of preventive phage therapy.”

Not only did they demonstrate the prophylactic phage therapy's effectiveness against an intracellular pathogen, but they also quantified its ability to eliminate fecal shedding. This is particularly important for Johne’s disease since fecal shedding and environmental contamination are a main driver of transmission. On-farm transmission continues as current diagnostics fail to detect infected animals before they show signs of illness, even though they are still infectious and shedding the bacteria.

"Our experimental data unequivocally demonstrate the potency of this approach in safeguarding against MAP infection, an aspect that has remained unexplored until now," says De Buck. “We anticipate a great interest from the dairy industry and animal health companies to further explore the practical application on farms.”

The outcomes of this research provide valuable and unprecedented insights into the potential of phage-based interventions against mycobacteria, contributing substantively to the growing field of phage therapy. This could open the door for protecting against other infectious diseases in production animals, safeguarding not just the animals affected, but also shielding producers and consumers from adverse economic and food security repercussions. The research team's initiative and resourcefulness bring us one step closer to understanding and combating infectious diseases through novel treatments.