The interaction between host demography and tuberculosis transmission: disease dynamics, control and evolution.

Lead Research Organisation: University of Cambridge
Department Name: Veterinary Medicine

Abstract

TB is the leading single cause of death in humans due to an infectious agent. Approximately 30% of the world's population is latently infected and 0.1% has active disease. TB is characterised by long-term asymptomatic infection that can progress to active disease years or decades after exposure. Active disease can produce a persistent cough, fever, weight loss and, if untreated, death in approximately 50% of cases. In recent years rates have escalated due to the interaction with the HIV epidemic and the emergence of drug resistant strains. TB affects many other mammals as well as humans. Bovine TB is endemic in many domestic cattle populations. Transmission to humans can occur via contaminated milk or direct contact. In Great Britain, bovine TB is one of the most complex and persistent problems facing the cattle industry, with an estimated annual cost of 90 million. Transmission of bovine TB between farms occurs via a combination of local infection and the movement of infected animals. While much less is understood about the natural history of disease in cattle, many of the principles involved in understanding TB spread apply to both humans and cattle. Mathematical models are used to predict how TB will spread in a population and the kind of interventions that might lead to eradication. Models include factors that are known to affect the spread of TB such as stress or overcrowding. Furthermore, progression rates are highly dependent on age of infection. This means that an ageing population is very different, in terms of TB, than a population with high birth rates. The effect of changing demography on TB spread has not been investigated in TB models, and so predictions about how to control the disease are not as accurate as they could be. This project will develop a new, comprehensive framework to understand the transmission dynamics and evolution of chronic diseases, with a particular focus on TB. The framework will be flexible to the needs of TB epidemiologists by incorporating transmission, age-dependent immune response, demographic changes and variation in genetic susceptibility.

Planned Impact

During the course of the fellowship, I propose to undertake a body of work that will advance current thinking about modelling and control of chronic diseases. The initial impact of the work will be aimed at the academic community through publishing articles in the modelling and interdisciplinary literature, attending conferences and establishing collaborations with researchers. This research is fundamentally interdisciplinary, and therefore will impact both theoretical and applied research. In particular, the new knowledge will be shared with infectious disease modellers, demographers, TB clinicians and epidemiologists, veterinarians and researchers studying bovine TB transmission in cattle and wildlife populations. I will maintain a web server with background information and major findings. This will include the framework and code for basic TB models, so that modelling can be included in field studies at an early stage by non-expert modellers. The advances in understanding TB population dynamics will have direct implications for public health and the control of livestock diseases and will contribute to maintaining the UK's position at the forefront of infectious disease modelling and disease control. Collaboration with the World Health Organization (WHO), the Health Protection Agency (HPA) and the Department for Environment, Food and Rural Affairs (Defra) will be an essential means of realising the maximum long-term health and economic benefits of this work. Promotion of my work in public spaces, such as at museums and online, will increase its access for a wide range of people. Presentations and posters at agricultural and countryside shows and events will improve the awareness of the research among farming communities and a presence at medical conferences and publication in medical journals will facilitate communication with the healthcare industry.

Publications

10 25 50
 
Description During my fellowship, I worked on methods to understand and quantify the transmission of tuberculosis and bovine tuberculosis. Using cattle movement data and bovine tuberculosis surveillance data from Great Britain, I demonstrated that a small percentage of farms cause the majority of new cases. I developed tools to quantify the age-specific risks of bovine tuberculosis in cattle in Great Britain and was able to show that young dairy and beef animals experience similar infection rates. I developed an axiomatic model of tuberculosis transmission between cattle and badgers that demonstrated how badgers can be essential for maintaining infection in cattle without being responsible for the majority of cases in cattle.
Exploitation Route My work is being developed by the Tuberculosis Modelling Consortium to provide a "plug-and-play" epidemic model for use by the Animal and Plant Health Agency.
More generally, I would like farmers to feel more empowered in controlling bovine tuberculosis in their herds.
Sectors Agriculture, Food and Drink,Healthcare

URL http://www.ellbp.net/research/bovinetb
 
Description The mathematical model and parameter inference methods developed during my fellowship (Brooks-Pollock, Roberts & Keeling "A dynamic model of bovine tuberculosis in Great Britain" Nature 511, 228231. doi:10.1038/nature13529.) are being used as a basis for further modelling work as part of a Tuberculosis Modelling Consortium established and funded by the Department for the Environment, Food and Rural Affairs (Defra).
First Year Of Impact 2014
Sector Agriculture, Food and Drink
Impact Types Policy & public services

 
Description Membership of Defra Tuberculosis modelling initiative
Geographic Reach National 
Policy Influence Type Citation in other policy documents
 
Description A study to design risk based bTB surveillance regimes in England and Wales
Amount £269,277 (GBP)
Organisation Department For Environment, Food And Rural Affairs (DEFRA) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2011 
End 09/2013
 
Description Charles Slater Award
Amount £2,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 08/2012 
End 09/2012
 
Description Development and testing of Operational Models of Bovine Tuberculosis in British Cattle and Badgers
Amount
Funding ID SE3290 
Organisation Department For Environment, Food And Rural Affairs (DEFRA) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2016 
End 09/2018
 
Description Tuberculosis Modelling Initiative 
Organisation Department For Environment, Food And Rural Affairs (DEFRA)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution The consortium is using my national scale model as a basis for the modelling work.
Collaborator Contribution Rowland Kao in Glasgow is the Principle Investigator.
Impact None to date
Start Year 2014
 
Description Article in Pioneer, the EPRSC magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Article in Pioneer about my work on tuberculosis in cattle and badgers.
Year(s) Of Engagement Activity 2013
 
Description Article in The Conversation 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Together with Ewan Harrison, I wrote an article for The Conversation on zoonotic infections.
Year(s) Of Engagement Activity 2013
URL https://theconversation.com/badger-cull-why-we-must-keep-a-close-eye-on-animal-health-16101
 
Description Interview on BBC Midlands Today 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Matt Keeling and I were interviewed on Midlands Today about a national TB model.
Year(s) Of Engagement Activity 2014
 
Description Interview on Countryfile on BBC1 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Myself and Professor Matt Keeling were interviewed on Countryfile on BBC1, where the results of our study were discussed. I received multiple emails and letters from people who had seen the programme, including from farmers and teachers interested in the area.
Year(s) Of Engagement Activity 2014
 
Description Interviews on BBC Radio 4 Farming Today 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed on Farming Today in 2014 about national-scale TB model and in 2016 about cattle-badger model.
Year(s) Of Engagement Activity 2014,2015
 
Description Invited Talk at IMA Mathematics 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact My presentation sparked lively discussion and requests from a couple of teachers for more information so that they could include it in classroom activities.
Year(s) Of Engagement Activity 2013
URL http://www.ima.org.uk/conferences/conferences_calendar/ima_mathematics_2013.cfm
 
Description Meet the Scientist event at the Birmingham Science Museum 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I organised a day event at the Birmingham Science museum where myself and colleagues from the London School of Hygiene and Tropical Medicine presented "The Science behind Influenza Epidemics".
Year(s) Of Engagement Activity 2011
URL http://www.birmingham.ac.uk/university/colleges/mds/events/2014/10/think-tank.aspx
 
Description Organiser of the Mentor Scheme at the European Conference of Mathematical and Theoretical Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I set up and ran the mentor scheme at an international conference. Many of the students reported that the meeting with a senior scientist improved their conference experience and future prospects.
Year(s) Of Engagement Activity 2011
 
Description Press briefing at the Science Media Centre 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Matt Keeling and I gave a presentation on our national scale TB model at the Science Media Centre.

Attendees
Claire Marshall - BBC News
Jamie Day - Animal Pharm
Damian Carrington - Guardian
Emily Beaumont - Press Association
Ben Spencer - Daily Mail
Laura Mulholland - BBC Newsnight
Alastair Driver - Farmer's Guardian
Alan Bullion - Agra Europe (Informa)

Recordings: https://db.tt/sAwmbSqP
Recording sent to Kate Kelland (Reuters), Tom Heap (Countryfile?), & Ben Webster (Times)

Media Enquiries
Ben Webster (Times) spoke to Ellen Brooks-Pollock and Matt Keeling

Briefing coverage
Guardian
http://www.theguardian.com/environment/2014/jul/02/tuberculosis-tb-threat-mass-cull-cattle-not-badgers-study

New Scientist
http://www.newscientist.com/article/dn25830-kill-cattle-not-badgers-to-halt-uks-tb-epidemic.html#.U7Q70LEYDm4

BBC News
http://www.bbc.co.uk/news/uk-england-28132627

Financial Times
http://www.ft.com/cms/s/0/42f48fda-0127-11e4-b94d-00144feab7de.html#axzz36KdznfQL

Farmers Guardian
http://www.farmersguardian.com/home/hot-topics/bovine-tb/defra-dismisses-research-questioning-badger-cull-value/65703.article

BBC News
http://www.bbc.co.uk/news/science-environment-28033649

Daily Mail
http://www.dailymail.co.uk/news/article-2678630/Culling-Britains-badgers-not-stop-spread-TB-cattle-killing-640-000-cows-year-will.html?ITO=1490&ns_mchannel=rss&ns_campaign=1490

Telegraph
http://www.telegraph.co.uk/earth/environment/10942274/Culling-cattle-not-badgers-only-way-to-stop-bovine-TB.html

Independent
Print only, NIB, p20
Year(s) Of Engagement Activity 2014
 
Description Royal Society Pairing Scheme 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact • One of 33 scientists selected for the scheme
• Develops links between scientists, parliamentarians and Civil Servants via a week in
Westminster and reciprocal visits
• Paired with Sarah Brown from the Health and Safety Executive
Year(s) Of Engagement Activity 2013,2014
 
Description School workshop on the Maths of culling badgers, Sir William Borlase's Grammar School, Marlow. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I was invited by Andrew Conlan to talk about the maths of culling badgers to maths A-level students at Sir William Borlase's Grammar School in
Marlow. A lively debate followed my talk and the students were interested in this application of Maths.
Year(s) Of Engagement Activity 2013
 
Description ScienceGrrl for International Women's Day, Science Museum, London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact As part of International Women's day, I took part in the ScienceGrrl event at the Science Museum in London. I spoke to museum visitors about my work.
Year(s) Of Engagement Activity 2013