Nav: Home

Cost and scale of field trials for bovine TB vaccine may make them unfeasible

June 07, 2018

Field trials for a vaccination to protect cattle against bovine tuberculosis (bovine TB) would need to involve 500 herds - potentially as many as 75,000-100,000 cattle - to demonstrate cost effectiveness for farmers, concludes a study published today in the journal eLife.

Instead, the researchers suggest that the scale and cost of estimating the effect of a vaccine on transmission could be dramatically reduced by using smaller, less expensive experiments in controlled settings - using as few as 200 animals.

Bovine TB is an infectious disease that affects livestock and wildlife in many parts of the world. In the UK, it is largely spread between infected cattle; badgers are also involved, transmitting to and receiving infection from cattle. Culls to keep badger populations small and reduce the likelihood of infecting cattle have proven controversial both with the public and among scientists.

The UK has a policy of 'test and slaughter' using the tuberculin test and slaughter of infected animals. A vaccine (BCG) exists, but can cause some vaccinated cattle to test positive falsely. As such, the vaccine is currently illegal in Europe. Researchers are trying to develop a so-called 'DIVA test' ('Differentiates Infected from Vaccinated Animals') that minimises the number of false positives, but none are yet licensed for use in the UK.

The European Union has said it would consider relaxing its laws against bovine TB vaccination if the UK government were able to prove that a vaccine is effective on farms. Any field trials would need to follow requirements set by the European Food Safety Authority (EFSA).

In research published today, a team of researchers led by the University of Cambridge has shown using mathematical modelling that satisfying two key EFSA requirements would have profound implications for the likely benefits and necessary scale of any field trials.

The first of these requirements is that vaccination must be used only as a supplement, rather than replacement, to the existing test-and-slaughter policy. But use of vaccination as a supplement means that a successful vaccine which reduces the overall burden and transmission of disease may nonetheless provide only limited benefit for farmers - false positives could still result in animals being slaughtered and restrictions being placed on a farm.

The second of the EFSA requirements is that field trials must demonstrate the impact of vaccination on transmission rather than just protecting individual animals.

The team's models suggest that a three year trial with 100 herds should provide sufficient to demonstrate that vaccination protects individual cattle. Such a trial would be viable within the UK. However, demonstrating the impact on vaccination on transmission would be almost impossible because the spread of bovine TB in the UK is slow and unpredictable.

If BCG were to be licensed for use in cattle in the UK, vaccination would be at the discretion of individual farmers. Farmers would have to bear the costs of vaccination and testing, as well as the period of time under restrictions if animals test positive. This means that they would be less interested in the benefit to individual cattle and more interested in the benefits at the herd level. Herd immunity is such that, even if the vaccine is not 100% effective in every individual animal, the vaccine has an overall protective effect on the herd.

Trying to demonstrate an economic benefit for farmers would prove challenging. Using their models, the researchers show that herd-level effectiveness would be exceptionally difficult to estimate from partially-vaccinated herds, requiring a sample size in excess of 2,000 herds. The number of herds required could be reduced by a 'three arm design' that includes fully-vaccinated, partially-vaccinated and unvaccinated control herds; however, such a design would still require around 500 fully-vaccinated herds and controls - presenting potential logistical and financial barriers - yet would still have a high risk of failure.

Instead, the researchers propose a natural transmission experiment involving housing a mixture of vaccinated and unvaccinated cattle with a number of infected cattle. Such an experiment, they argue, could provide robust evaluation of both the efficacy and mode of action of vaccination using as few as 200 animals. This would help screen any prospective vaccines before larger, more expensive and otherwise riskier trials in the field.

"We already know that the BCG vaccine has the potential to protect cattle from bovine TB infection," says Dr Andrew Conlan from the Department of Veterinary Medicine at the University of Cambridge, the study's first author. "Our results highlight the enormous scale of trials that would be necessary to evaluate BCG alongside continuing testing in the field.

"Such trials would be hugely expensive, and it isn't even clear whether enough farms could be recruited. This scale could be dramatically reduced by using smaller scale natural transmission studies."

Based on current knowledge of the likely efficacy of BCG, the researchers say their models do not predict a substantial benefit of vaccination at the herd level when used as a supplement to ongoing test-and-slaughter. Ruling out the use of vaccination as a replacement, rather than a supplement, to test-and-slaughter will inevitably limit the effectiveness and perceived benefits for farmers.

"If we could consider replacing test-and-slaughter with vaccination, then the economics becomes much more attractive, particularly those in lower income countries," says Professor James Wood, Head of Cambridge's Department of Veterinary Medicine. "Then, we would no longer need to carry out expensive testing, but could instead rely on passive surveillance through the slaughterhouses."
The study was funded by the UK Department for Environment, Food and Rural Affairs (Defra) and the Alborada Trust


Conlan, AJK, et al. The intractable challenge of evaluating cattle vaccination as a control for bovine Tuberculosis. eLife; 5 June 2018; DOI: 10.7554/eLife.27694.001

University of Cambridge

Related Vaccination Articles:

Religion associated with HPV vaccination rate for college women
A survey of female college students finds 25% had not been vaccinated for HPV and religion may be a contributing factor.
Measles vaccination: 'All for one and one for all'
A commentary by researchers addresses the specter of clinical, ethical, public health and legal concerns that have been raised because of the recent measles outbreaks in New York.
New single vaccination approach to killer diseases
Scientists from the University of Adelaide's Research Centre for Infectious Diseases have developed a single vaccination approach to simultaneously combat influenza and pneumococcal infections, the world's most deadly respiratory diseases.
Vaccination may help protect bats from deadly disease
A new study shows that vaccination may reduce the impact of white-nose syndrome in bats, marking a milestone in the international fight against one of the most destructive wildlife diseases in modern times.
Parents reassured febrile seizures following vaccination not dangerous
New University of Sydney research finds that febrile seizures after vaccination are rare, not serious and are no different to febrile seizures due to other causes such as from a virus.
Is maternal vaccination safe during breastfeeding?
In light of the continuing anti-vaccination movement, a provocative new article provides a comprehensive overview of the potential risks of vaccinating breastfeeding women.
Flu vaccination keeps COPD patients out of the hospital
A new study published in the January issue of CHEST® establishes that patients with chronic obstructive pulmonary disease (COPD) face heightened risks of death, critical illness, and hospitalization if they develop the flu and demonstrates the beneficial effects of influenza vaccination.
Addressing expected challenges after resumption of HPV vaccination
Researchers at Osaka University present measures for reducing a risk of uterine cervical cancer that increased by the suspension of the Japanese government recommendation for the Human Papillomavirus (HPV) vaccination and for promoting HPV vaccination after its resumption
Research explains public resistance to vaccination
A new study explains why it is so hard to increase public vaccination levels even when evidence indicates that vaccines are safe and beneficial.
Childhood vaccination exemptions rise in parts of the US
Non-medical exemptions from childhood vaccinations are rising in some areas of the United States, creating a risk of vaccine-preventable disease outbreaks, argue Peter Hotez, Melissa Nolan, Jackie Nolan, and Ashish Damania in a Policy Forum article in PLOS Medicine.
More Vaccination News and Vaccination Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.