TB vaccine may enable elimination of the disease in cattle by reducing its spread
The research, led by the University of Cambridge and Penn State University, improves prospects for the elimination and control of bovine tuberculosis (TB), an infectious disease of cattle that results in large economic costs and health impacts across the world.
This is the first study to show that BCG-vaccinated cattle infected with TB are substantially less infectious to other cattle. This remarkable indirect effect of the vaccine beyond its direct protective effect has not been measured before.
The spillover of infection from livestock has been estimated to account for about 10% of human tuberculosis cases. While such zoonotic TB (zTB) infections are most commonly associated with gastro-intestinal infections related to drinking contaminated milk, zTB can also cause chronic lung infections in humans. Lung disease caused by zTB can be indistinguishable from regular tuberculosis, but is more difficult to treat due to natural antibiotic resistance in the cattle bacteria.
TB remains endemic in many countries around the world, including in Europe and the Americas, where its control costs farmers and taxpayers hundreds of millions of dollars each year.
The study is published today in the journal Science.
In the study, carried out in Ethiopia, researchers examined the ability of the vaccine, Bacillus Calmette-Guérin (BCG), to directly protect cattle that receive it, as well as to indirectly protect both vaccinated and unvaccinated cattle by reducing TB transmission. Vaccinated and unvaccinated animals were put into enclosures with naturally infected animals, in a novel crossover design performed over two years.
“Our study found that BCG vaccination reduces TB transmission in cattle by almost 90%. Vaccinated cows also developed significantly fewer visible signs of TB than unvaccinated ones. This suggests that the vaccination not only reduces the progression of the disease, but that if vaccinated animals become infected, they are substantially less infectious to others,” said Andrew Conlan, Associate Professor of Epidemiology at the University of Cambridge’s Department of Veterinary Medicine and a corresponding author of the study.
Using livestock census and movement data from Ethiopia, the team developed a transmission model to explore the potential for routine vaccination to control bovine tuberculosis.
“Results of the model suggest that vaccinating calves within the dairy sector of Ethiopia could reduce the reproduction number of the bacterium — the R0 — to below 1, arresting the projected increase in the burden of disease and putting herds on a pathway towards elimination of TB,” Conlan said.
The team focused their studies in Ethiopia, a country with the largest cattle herd in Africa and a rapidly growing dairy sector that has a growing burden of bovine tuberculosis and no current control program, as a representative of similarly situated transitional economies.
“Bovine tuberculosis is largely uncontrolled in low- and middle-income countries, including Ethiopia,” said Abebe Fromsa, associate professor of agriculture and veterinary medicine at Addis Ababa University in Ethiopia and the study’s co-lead author. “Vaccination of cattle has the potential to provide significant benefits in these regions.”
“For over a hundred years, programs to eliminate bovine tuberculosis have relied on intensive testing and slaughtering of infected animals,” said Vivek Kapur, professor of microbiology and infectious diseases and Huck Distinguished Chair in Global Health at Penn State and a corresponding author of the study.
He added: “This approach is unimplementable in many parts of the world for economic and social reasons, resulting in considerable animal suffering and economic losses from lost productivity, alongside an increased risk of spillover of infection to humans. By vaccinating cattle, we hope to be able to protect both cattle and humans from the consequences of this devastating disease.”
Professor James Wood, Alborada Professor of Equine and Farm Animal Science in the University of Cambridge’s Department of Veterinary Medicine, noted that despite TB being more prevalent in lower-income countries, the United Kingdom, Ireland and New Zealand also experience considerable economic pressures from the disease which continues to persist despite intensive and costly control programs.
Wood said: “For over twenty-years the UK government has pinned hopes on cattle vaccination for bovine tuberculosis as a solution to reduce the disease and the consequent costs of the controls. These results provide important support for the epidemiological benefit that cattle vaccination could have to reduce rates of transmission to and within herds.”
This research was supported by The Bill & Melinda Gates Foundation, as well as the Biotechnology and Biological Sciences Research Council; Foreign, Commonwealth and Development Office; Economic & Social Research Council; Medical Research Council; Natural Environment Research Council; and Defence Science & Technology.
Reference: Fromsa, A. et al: ‘BCG vaccination of cattle reduces transmission of bovine tuberculosis, improving the prospects for elimination.’ Science, March 2024. DOI: 10.1126/science.adl3962
Vaccination not only reduces the severity of TB in infected cattle, but reduces its spread in dairy herds by 89%, research finds.
Our study suggests that vaccination not only reduces the progression of the disease, but that if vaccinated animals become infected, they are substantially less infectious to others.Andrew ConlanGetty/ kamisokaHerd of cows in a grassy field
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New Cambridge-developed resources bring infectious diseases into the maths classroom
From measles and flu to SARS and COVID, mathematicians help us understand and predict the epidemics that can spread through our communities, and to help us look at strategies that we may be able to use to contain them.
The project, called Contagious Maths, was led by Professor Julia Gog from Cambridge’s Department of Applied Mathematics and Theoretical Physics (DAMTP), and was supported by a Rosalind Franklin Award from the Royal Society.
The curriculum-linked resources will give students between the ages 11 and 14 the opportunity to join researchers on the mathematical frontline to learn more about infectious disease spread, along with interactive tools to try mathematical modelling for themselves. Teachers receive full lesson plans, backed up by Cambridge research.
“I’ve always loved maths. I was lucky enough to have amazing teachers at sixth form who challenged me and were 100% behind me pursuing maths at the highest level, but maths as it’s taught in school can be highly abstract, so students often wonder what the point of maths even is,” said Gog, who is also Director of the Millennium Maths Project. “This is something I’m trying to help with now: to offer a glimpse from school to the research world to see the role mathematics can play in tackling important real-world problems.”
The Contagious Maths project introduces mathematical modelling; explores how mathematicians can model the spread of disease through a population and the type of questions we might think about when looking at models; and gives an insight into what mathematics researchers working on these real-life problems actually do.
“I’ve been engaged in outreach for many years at Cambridge, and the Contagious Maths project grew out of discussions with colleagues who have expertise in reaching school-age children,” said Gog. “The 11-14 age group we are targeting is a real crunch point for retaining girls in maths, and future female mathematicians. What exactly happens is complex and multifaceted, but this is a period when people form their views on how they fit with maths and science.
“Many of them disengage, as it can seem that maths at school is utterly disconnected from the real world. It can also be a time when maths appears very starkly right or wrong, whereas any research mathematician can tell you it’s always so much more subtle that than, and therefore so much more interesting!”
Gog hopes the Contagious Maths resources might be able to help, as they are designed to be used in regular school lessons, and cover a topic with clear real-world importance.
“The maths is never black and white in this field: there are always ways to challenge and develop the models, and some tricky thinking to be done about how the real epidemics and the simulations are really related to each other,” she said. “I suspect some students will find this frustrating, and just want maths to be algorithmic exercises. But some will be intrigued, and they are the ones we are trying to reach and expose to this larger world of applied maths research.”
Contagious Maths also provides teachers with all the ideas and tools they need, so they have at their fingertips all they need to deliver these lessons, even if they have no experience with research mathematics. “We hope this project will help these teachers to bring in the wider view of mathematics, and we hope it inspires them too,” said Gog. “It’s been really fun developing these resources, teaming up with both NRICH and Plus to make the most of our combined expertise.”
Maths teachers can attend a free online event on 20 March to learn more about the project.
In addition to the school resources, Gog and her colleagues have designed another version of Contagious Maths for a more general self-guided audience, which will work for students older than 14 or anyone, of any age, who is interested in learning about mathematical modelling.
“The paradox between the cleanness and precision of mathematics, and the utter hot mess of anything that involves biological dynamics across populations – like an outbreak of an infectious disease, is what intrigued me to stay in mathematics beyond my degree, and to move into research in mathematical biology,” said Gog. “Elegant theoretical ideas can tell us something valuable and universal about mitigating the devastating effects of disease on human and animal populations. Super abstract equations can hold fundamental truths about real-world problems - I don't think I will ever tire of thinking about that.”
Adapted from a Royal Society interview with Professor Julia Gog.
Cambridge mathematicians have developed a set of resources for students and teachers that will help them understand how maths can help tackle infectious diseases.
Orbon Alija via Getty ImagesAerial view of crowd connected by lines
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.