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Fighting TB on Many Fronts-The Newton Fund MRC-DBT

MRC-DPT funded Centre Partnership betweenthe National Institute for Research in Tuberculosis, Chennai and the University of Cambridge

There are few places more suitable for the proposed work than India. According to the World Health Organization, India is home to almost one in four of all worldwide cases of TB, with over two million newly-diagnosed cases in 2014.

An expansion of Cambridge's on-going collaboration with India has become possible through the recent award of a £2 million joint grant from the UK Medical Research Council (MRC) and the Department of Biotechnology (DBT) in India, which will enable the exchange of British and Indian researchers.

Sharon Peacock.jpgProfessor Sharon Peacock, Professor of Clinical Microbiology, Department of Medicine, University of Cambridge

For Professor Sharon Peacock, the UK lead on the proposal, this means an opportunity to train a new cohort of early career researchers in an environment where they will have access to outstanding scientific facilities and training, at the same time as becoming familiar with the clinical face and consequences of TB for people in India.

“India is home to a large pool of talented young people with the potential to help fight back against this deadly disease,” says Peacock. “Developing a close collaboration between Cambridge and Chennai involving two-way traffic of scientists and ideas is an exciting opportunity to start to tap into this.”

Professor Peacock is Co-lead with Professor Soumya Swaminathan, of Project 1 of DBT-MRC project.

Because the drug regimen to fight the disease lasts so long, many patients do not take the full course of their medicines. Because TB evolves through ‘polymorphisms’ – spontaneous changes in the letters of its DNA to create variants. If the TB is allowed to relapse, it can evolve drug resistance.

 These patterns of resistance can be detected using genome sequencing – reading the DNA of the bacteria. Prof. Peacock believes this technique may be able to help doctors more easily diagnose drug-resistance in patients and is the subject of Project 1 of DBT-MRC project.

 “TB is very slow to grow in the laboratory, which means that testing an organism to confirm which antibiotics it is susceptible or resistant to can take several weeks, especially in the case of more resistant strains,” she says. “There is increasing evidence that antibiotic resistance can be predicted from the genome sequence of the organism, and we want to establish and evaluate this technology in India, where it is needed.”

Not only that, but it is one of the countries that has seen an increase in the number of cases of drug-resistance to TB – including ‘multi-drug’ resistant, and even more worrying, ‘extreme’ drug resistant, strains of TB against which none of our first- and second-line drug treatments work. In part, this increase reflects improved access to diagnostic services, but the situation highlights why new approaches to tackling the disease are urgently needed, says Professor Soumya Swaminathan, Director of NIRT and the India lead in the collaboration.

Professor Soumya Swaminathan SOUMYA-ONLINE_1659039e.jpg

Director, National Institute for Research in Tuberculosis (formerly the Tuberculosis Research Centre), Chennai

Adjunct Associate Clinical Professor, Dept. of Public Health and Family Medicine at Tufts University School of Medicine

 “TB is very much associated with poverty and all the risk factors that go with it,”  says Prof Swaminathan. “When people are living in very crowded conditions, when they’re malnourished, TB is going to continue to spread. This is happening in the slums of Mumbai, for example, where we’re seeing a mini-epidemic of multi-drug resistant TB. Unless we see a rapid improvement in the living standards of people we’re not going to see very major effect. There’s only so much we can do biomedically.”

MRC-DPT Research Areas and Teams

Project 1: Bacterial genomics as a diagnostic tool in drug-resistant TB (Sharon Peacock, Estee Torok, Uma Devi Ranganathan, Sujatha Narayanan)

Project 2: New drug targets for TB through prediction/investigation of impact of resistance mutations  (Sir Tom Blundell, Indian visiting fellows)

Project 3: Population based study of gene repertoire associated with drug tolerance and their in vivo expression (Lalita Ramakrishnan, Uma Devi Ranganathan, Siva Kumar)

Project 4: Host directed therapy through autophagy stimulation (Andres Floto, Siva Kumar)

Project 5: Manipulating T cell exhaustion: new therapies to improve outcomes in resistant TB (Ken Smith, Alena Srinivasan, Padmapriyadarsini Chandrasekaran, Annapurna Vyakarnam)

Project 6 Clinical cohorts and repositories (Padmapriyadarsini Chandrasekaran, Sujatha Narayanan, Estee Torok) Two new longitudinal prospective cohorts will be recruited for the current proposal to support the 5 proposed projects described below: (i) 50 patients with pulmonary MDR-TB (with and without additional drug resistance); and (ii) 100 patients with newly diagnosed drug-susceptible pulmonary TB (DS-TB).

 

Research Teams

The National Institute of Research in Tuberculosis India

Uma Devi Ranganthan, Alena Srinivasan,S Siva Kumar, Sujatha Narayanan, Padmapriyadarsini Chandrasekaran,Annapurna Vyakarnum

University of Cambridge

Sharon Peacock, Lalita Ramakrishnan, Sir Tom Blundell, Kenneth Smith, R. Andres Floto, M. Estee Torok

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