Tuberculosis
Macrophages engulfing mycobacterium tuberculosis
Tuberculosis (TB) is a disease caused by a bacterium, Mycobacterium tuberculosis (M.tb), and is found worldwide. In 2019 10 million people developed TB and 1.4 million died, making TB the greatest global infectious disease cause of death, killing more people every year than HIV or malaria.
Aside from causing death TB impairs general health, resulting in reduced economic productivity and increased social and medical burdens on families. The World Health Organisation estimates 100 million disability adjusted life years are lost due to TB in India alone. The average total cost to a patient with TB in a low/middle-income country is US$538-1268, which is equivalent to a year’s wages for many sufferers. Furthermore, animal disease such as bovine (cow) TB also has a very significant effect on people’s livelihoods and the economic development of low and middle-income countries.
Where is TB found?
TB occurs in every part of the world. In the UK, where TB used to kill 1 in 4 people in Victorian times, only 5,000-6,000 people now develop TB each year. TB is a disease of poverty. The highest rates today are in sub-Saharan Africa, in countries such as South Africa (world map of TB disease).
Around one-third of the world’s population is latently infected with M.tb, which means they have been infected but do not yet have active TB disease. Latently infected people have a 10% chance of developing active TB during their lifetime, and becoming ill. This risk increases if they are also infected with HIV.
Mycobacterium tuberculosis (credit: CDC)
How is TB spread?
TB is spread by inhaling bacteria that have been coughed, sneezed or spat into the air.
What are the symptoms of TB?
TB usually affects the lungs causing symptoms such as coughing, fever, tiredness and weight loss, but it can also affect other parts of the body such as the spine and brain (NHS symptoms page). Eventually TB leads to death.
Is TB curable?
TB is curable but drug-resistant strains of the bacteria are increasing (map). Treatment takes six months, is very costly, and can have unpleasant side effects, while treatment of drug resistant strains of M.tb can take up to two years. So developing a vaccine that could prevent TB infection is an important global public health goal - reducing global TB rates by 90% by 2030 is UN Sustainable Development Goal #3.
Vaccines against TB
The current TB vaccine is called BCG (Bacille Calmette-Guérin). BCG has been administered globally to several billion people, but it is over 90 years old and does not protect well against pulmonary (lung) TB. Pulmonary TB has the highest mortality and morbidity rates, so an improved vaccine is essential.
VALIDATE
At the VALIDATE Network, by bringing together TB researchers from around the world we hope to speed up progress towards an improved vaccine against this deadly disease.
Further Information:
‘Exposed: The Race Against TB’ – informative and interesting short films about TB and TB research
Medicins Sans Frontieres (MSF) - information and videos
World Health Organisation – Status of the Global TB Epidemic and Response infographic
World Health Organisation - End TB Strategy document
Natural variation of the bovine lymph node microenvironment and its possible effect on BCG immunogenicity
Led by Dr Lucia Biffar (University of Oxford, UK), with Dr Bernardo Villarreal-Ramos (APHA, UK) and Prof Tracy Hussell (University of Manchester, UK)
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Enhancing BCG efficacy: the Social Technology Lab Initiative
Led by Assist Prof Delia Boccia (LSHTM, UK), with Dr Jenn Dowd (KCL, UK), and Prof Helen Fletcher (LSHTM, UK)
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Establishment of a functional assay panel to evaluate the role of antibodies in defence against melioidosis and tuberculosis
Led by Dr Panjaporn Chaichana (MORU, Thailand), with Prof Susanna Dunachie (University of Oxford, UK), and Prof Helen Fletcher (LSHTM, UK)
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Overcoming innate immune tolerance in the respiratory tract for optimal vaccine design
Led by Dr Rajko Reljic (SGUL, UK) with Prof Tracy Hussell (University of Manchester, UK)
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How do functional and metabolic characteristics of trained monocytes affect their anti-bacterial activity?
Led by Asst Prof Steven Smith (LSHTM, UK), with Dr Javier Sanchez-Garcia (Instituto Politécnico Nacional, Mexico), Prof Jo Prior (dstl, UK), and Prof Gregory Bancroft (LSHTM, UK)
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Vaccines to target people with diabetes: characterising the pathways of immune response to M. tuberculosis and B. pseudomallei in people with diabetes compared to non-diabetics
Led by Prof Susanna Dunachie (University of Oxford, UK), with Assistant Prof Jacqueline Cliff (LSHTM, UK), and Prof Gregory Bancroft (LSHTM, UK)
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Identification of Leishmania donovani and Mycobacterium tuberculosis- derived proteins on the surface of infected macrophages that are associated with ADCC induction
Led by Dr Mohamed Osman (University of York, UK), with Prof Paul Kaye (University of York, UK), Dr John Pearl (University of Leicester, UK) and Prof Andrea Cooper (University of Leicester, UK)
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Identification of latency associated antigens and biosignatures associated with Mycobacterium tuberculosis
Dr Jomien Mouton (University of Stellenbosch, South Africa) - VALIDATE Fellowship
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Characterising the BCG-induced antibody response to inform the design of improved vaccines against M.tuberculosis, M.leprae and M.bovis
Dr Rachel Tanner (University of Oxford, UK) - VALIDATE Fellowship
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Metabolic reprogramming of skin microenvironment for improved BCG vaccine efficacy
Led by Titular Prof Francisco Javier Sánchez-García (Instituto Politécnico Nacional, Mexico), with Dr Steven Smith (LSHTM, UK), Dr Barbara Kronsteiner-Dobramysl (University of Oxford, UK) and Prof Hazel Dockrell (LSHTM, UK)
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Development of an RNA based vaccine against Mycobacterium tuberculosis
Led by Dr Rhea Coler (IDRI, USA), with Prof Helen Fletcher (LSHTM, UK)
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Developing a mouse model of diabetes to evaluate vaccines for TB and melioidosis
Led by Dr Elena Stylianou (University of Oxford, UK), with Prof Helen McShane (University of Oxford, UK), Assoc Prof Susanna Dunachie (University of Oxford, UK), Assoc Prof Paul Brett (University of Nevada, USA), Dr Barbara Kronsteiner-Dobramysl (University of Oxford, UK) and Dr Panjaporn Chaichana (MORU, Thailand)
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Cross protection against TB by attenuated Mycobacterium ulcerans strain 5114
Led by Dr Justice Boakye-Appiah (SGUL, UK), with Dr Rajko Reljic (SGUL, UK) and Dr Tufária Mussá (Eduardo Mondlane University, Mozambique)
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Characterising the cellular immunity and metabolic response to Mycobacterium tuberculosis and Burkholderia pseudomallei in Indian patients for vaccine design
Led by Prof Chiranjay Mukhopadhyay (Manipal Academy of Higher Education, India), with Prof Susanna Dunachie (University of Oxford, UK) and Prof Mitali Chatterjee (IPGMER, India)
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T cell receptor sequencing to identify correlates of protection in human tuberculosis vaccine studies
Led by Dr Gabriele Pollara (UCL, UK), with Prof Mahdad Noursadeghi (UCL, UK), Assoc Prof Susanna Brighenti (Karolinska Institutet, Sweden), Assoc Prof Senait Ashenafi (Addis Ababa University, Ethiopia) and Prof Benny Chain (UCL, UK)
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An ex vivo model for understanding the impact of vaccination on Mycobacterial persister populations
Led by Prof Samantha Sampson (Stellenbosch University, South Africa), with Asst Prof Andrea Zelmer (LSHTM, UK) and Dr Jomien Mouton (Stellenbosch University, South Africa)
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Investigating the BCG-induced Natural Killer (NK) cell response in cattle and humans
Led by Dr Iman Satti (University of Oxford, UK), with Asst Prof Stephen Cose (UVRI, Uganda), Prof Helen McShane (University of Oxford, UK), Prof Alison Elliott (UVRI, Uganda) and Prof Jayne Hope (University of Edinburgh, UK)
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Cytomegalovirus as a risk factor for TB and leishmaniasis
Led by Dr Lisa Stockdale (University of Oxford, UK), with Dr Robindra Basu Roy (LSHTM, UK), Dr Vivian Tamietti Martins (Federal University of Minas Gerais, Brazil), Assoc Prof Eduardo Coelho (Federal University of Minas Gerais, Brazil), and Prof Helen Fletcher (LSHTM, UK)
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Innovative tools to measure mycobacterial antigen expression in tissue
Led by Dr Simon Waddell (University of Sussex, UK), with Dr Javier Salguero Bodes (PHE, UK), Prof Gobena Ameni (Addis Ababa University, Ethiopia), Dr Sally Sharpe (PHE, UK) and Dr Ann Rawkins (PHE, UK)
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