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Available under license: http://creativecommons.org/licenses/by-nc-nd/2.5/ TB Centre London School of Hygiene & Tropical Medicine Keppel Street, London WC1E 7HT Switchboard: +44 (0)20 7636 8636 tb centre [email protected] http://tb.lshtm.ac.uk Twitter: @LSHTM_TB November 2015 www.lshtm.ac.uk Cover image: active case finding in Blantyre, Malawi, courtesy of Liz Corbett Improving health worldwide TB Centre Biennial Report 2015 1 Biennial Report 2015 2 Foreword: working to tackle the intractable About the TB Centre challenges of tuberculosis Despite significant progress in recent decades, tuberculosis continues to be a major TB kills more people worldwide than any other disease. In 2014, cause of mortality in many parts of the world, and in some areas, even in high-income 9.6 million people contracted TB and 1.5 million died from the countries including the UK, it is on the rise once more. This resurgence is caused disease. However, the number of people with a new diagnosis by two major challenges: people living with HIV, which greatly increases the risk of of TB has fallen by an average of 1.5% per year since 2000, developing active TB disease, and the emergence of multi drug-resistant forms of TB and ending the disease by 2030 is among the health targets that are extremely difficult to treat. of the newly adopted Sustainable Development Goals. This is a daunting task, but if researchers, governments, NGOs, industry Our School has for many years been at the forefront of tuberculosis research, diagnosis and funders respond now, working together we can achieve it. and treatment, working in collaboration with government agencies, universities and civil society partners across more than 70 projects in around 40 countries worldwide. The TB Centre at the London School of Hygiene & Tropical Medicine brings together more than 120 laboratory scientists, In recent years, the TB Centre at the School has become established as a collaborative clinicians, epidemiologists, statisticians, public health specialists hub to further develop and co-ordinate this work. Thanks to the leadership of David Helen Fletcher Katherine Fielding and policy-makers. Our shared purpose is to reduce the global Moore, and now Helen Fletcher, the Centre is growing to encompass all aspects of burden of TB, through high quality research, education and research from laboratory science in host and pathogen biology, deciphering the genetic knowledge translation. code of drug resistant strains, to implementing new control strategies. Collaboration We work in more than 20 countries with high prevalence of TB This report highlights some of the projects, partnerships and areas in which the Centre Innovation across Asia, Africa and Latin America, and our researchers are is engaged. There is much to do, and as always the biggest challenge is to persuade strongly integrated with local academic institutions, governments Through consultancy work, research meetings, seminars and governments and funders to work together and act strategically to build effective health and international organisations. systems and services. TB has throughout history been closely linked with poverty, and journal clubs, we disseminate our work and generate new ideas. its control will come through sustained public health and socio-economic interventions Members of the TB Centre are global leaders in areas including: that improve people’s quality of life. clinical trial design Investing in the future I hope you will be inspired by what you read here to support the work of the TB Centre epidemiology We are committed to training the next generations of TB and join us in the common goal to understand, control, and ultimately eliminate this tracing of TB transmission using molecular tools researchers, and have an active student community within the TB disease. host-pathogen interactions Centre. Our collective goal is to generate new knowledge, and to development and implementation of new diagnostics transfer the highest quality research into policy and practice, and mathematical modelling ultimately real-world impact. We invite you to join us. health economics Baron Peter Piot Director and health systems research Helen Fletcher, Director, TB Centre Professor of Global Health Katherine Fielding, Deputy Director, TB Centre London School of Hygiene & http://tb.lshtm.ac.uk Tropical Medicine Twitter: @LSHTM_TB This publication was collated and edited by Steve Smith, Helen Fletcher, David Moore and Patrick Wilson, November 2015. Contents 1 About the TB Centre 2 Clinical trials: towards effective diagnosis and treatment 3 TBVAC2020: the quest for new and improved TB vaccines 4 - 5 TB Centre activities around the world 6 Towards better control of HIV- related TB 7 TB Modelling and Analysis Consortium 8 Interactions between TB and diabetes 9 Taught courses and research degrees relating to TB Staff collecting TB data electronically, Staff at TB Centre retreat in Canterbury, November 2015, by Kristian Godfrey courtesy of ZAMSTAR (see page 6) 2 Biennial Report 2015 1 Clinical trials: towards effective diagnosis and treatment The launch of the TBVAC2020 consortium, courtesy of The TB Vaccine Initiative Progress towards rapid and reliable diagnosis followed by TB Fast Track: evaluating empirical TB effective drug treatment is vital in the effort to control The quest for new and improved TB vaccines tuberculosis. TB Centre investigators have been awarded treatment for people with HIV funding for a number of major clinical trials which aim to effect TB is the most leading cause of death among people with HIV The current vaccine against tuberculosis, Bacille Calmette Guerin Standardised pre-clinical models for this progress. worldwide, and limited data suggest that this remains true of (BCG) is nearly a century old and does not provide effective people starting antiretroviral therapy. However, the diagnosis of protection against TB, especially in high incidence settings where candidate TB vaccine evaluation TB is difficult and may be missed altogether. People with low CD4 it is most needed. To eventually eliminate TB, we need a new, This component of the TBVAC2020 research programme at cell counts in particular are less likely to be diagnosed using highly efficacious vaccine. The TB Vaccine Initiative consortium the School will provide standardised head-to-head testing of sputum-based tests, because of low mycobacterial concentration (TBVAC2020) has been granted 24.6 million euros from the candidate TB vaccines. Testing for both safety and efficacy will or inability to produce sputum. European Horizon 2020 programme and other government be performed using immune deficient mice. TB Fast Track is a cluster-randomised trial that aims to evaluate sources to advance new TB vaccine candidates from discovery TB Centre members: Gregory Bancroft, Felipe Cia the effects of targeted empirical TB treatment on early mortality to clinical development. Three TB Centre principal investigators, in people with HIV accessing antiretroviral therapy in clinics in Hazel Dockrell, Gregory Bancroft and Helen Fletcher, are leading Preclinical Model South Africa. The intervention uses a point-of-care technology- on three separate projects as part of a consortium of 40 Development based algorithm to rapidly identify individuals at high risk, and research institutes, pioneering innovative approaches to vaccine ensure they start TB treatment, followed by antiretroviral therapy. development. People are often affected by Mortality in the intervention group will be compared to that conditions that increase their among adults managed according to standard practice based on risk of developing TB. These South African guidelines. Discovery and development of TB conditions include HIV, obesity TB Fast Track is funded by a UK Medical Research Council, biomarkers of protection and diabetes. New animal models will be developed to Department for International Development and Wellcome Trust The Biomarkers of Protection work package of TBVAC2020 aims better reflect these human Global Clinical Trials Scheme grant award of £3.2 million. to optimise the measurement of candidate biomarkers and conditions that are associated Principal Investigator: Alison Grant; TB Centre co-investigators: develop methods such as the Mycobacterial Growth Inhibition Rapid urine-based screening for TB with increased TB disease risk. Katherine Fielding, Anna Vassall assay, which indicate the level of immunity a person has against This will improve our chances of to reduce AIDS-related mortality in TB. Host immune responses will be correlated with TB disease identifying vaccines to protect hospitalised patients in Africa risk and the effect of helminth worm infections on mycobacterial The XTEND study: evaluating Xpert MTB/ vulnerable populations. Post-mortem studies show that TB is the cause of between growth inhibition will be analysed. TB Centre members: Helen one-third and two-thirds of adult HIV/AIDS-related deaths RIF as a first line TB test in South Africa TB Centre members: Helen Fletcher, Andrea Zelmer, Hazel Fletcher, Andrea Zelmer recorded in health facilities in sub-Saharan Africa. However, The XTEND study evaluated the impact of the new diagnostic