Projects

Projects starting in 2013

Title

PanBIOME: PanACEA Biomarkers Expansion programme.

Lead Prof Tim McHugh
Participants

Dr Isobella Honeyborne, Mr Robert Hunt

Funding Body EDCTP
Project start/end dates 01/01/2013 – 01/01/2014
Description: 200 characters max.

There is a pressing need to develop new drugs for tuberculosis but current methodologies to trial these are slow and expensive. Additionally, the facilities to perform tuberculosis clinical trials in high burden counties are insufficient to make progress rapidly. We aim to address this problem in this application. Alongside our MAMS study that is funded through the EDCTP we will evaluate the Molecular Bacterial Load assay in comparison with the GeneXpert for their ability to detect the response to anti-tuberculosis therapy. By use of a range of modelling techniques it may become possible to reduce sample size in future clinical trials. In addition we will investigate the ability of resuscitation promotion factor (rpf) to improve the accuracy of viable count assessment using the MGIT platform. Finally, we will build on the successful PanACEA consortium and add two new sites that will be available to deliver clinical trials in the future this will be linked to comprehensive training and the development of South-South support network for future biomarker studies. The PANBIOME project provides a balanced portfolio clinical evaluation of new techniques with capacity development to strengthen centres in sub-Saharan Africa.

Contact for further information Prof Tim McHugh
Website
http://panacea-tb.net/
Title TB transmission in rural KwaZulu-Natal
Lead Prof Marie-Louise Newell
Participants Dr Tom Yates, Prof Frank Tanser, Prof Ibrahim Abubakar
Funding Body KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban
Project start/end dates  June 2013 - March 2014
Description: 200 characters max.

Most TB in high burden settings is a result of recent transmission outside the home. This study, based at the Africa Centre for Health and Population Studies, KwaZulu-Natal, South Africa, will characterise risk factors for TB transmission. The setting is a rural community with a high TB burden in the context of a generalised HIV epidemic.

TB infection will be measured in a tuberculin skin test survey, recruiting 6 and 7 year olds attending local primary schools. This will allow annual risk of TB infection to be calculated.

These data will be linked to these children’s records in the Africa Centre household surveillance programme, a rich longitudinal dataset focussing on health and socio-demographics.

Risk factor and spatial analyses will be conducted with a focus on the association between use of particular indoor public spaces and TB infection.

Contact for further information t.yates[at]ucl.ac.uk
Title

The HALT Study

Lead Ibrahim Abubakar and Helen Stagg
Funding Body DH Policy Research Programme
Project start/end dates 2013 to 2015
Description: 200 characters max.

This programme of work includes two trials; to assess potential improvement in treatment completion with a 12 dose weekly rifapentine and isoniazid compared to daily rifampicin and isoniazid and to assess the whether peer support can improve engagement with clinical care following the detection of hepatitis C virus infection.

Contact for further information h.stagg@ucl.ac.uk

Projects started in 2012

Title PreDiCT-TB: Model-based preclinical development of anti-tuberculosis drug combinations
Lead Prof Tim McHugh
Participants Dr Dimitrios Evangelopolous
Funding Body Innovative Medicines Initiative (IMI) and European Federation of Pharmaceutical Industries and Associations (EFPIA)
Project start/end dates 01/05/2012 to 01/05/2017
Description: 200 characters max.

The PreDiCT-TB consortium aims to determine and validate improved methods for pre-clinical drug discovery and development. This will be achieved by integrating multiple in vitro and in vivo models to predict the efficacy of different drug combinations against TB in an aim to identify an optimized decision pathway for the best combination regimens to progress into clinical trials. This a collaborative venture between 22 participants from all around Europe that also includes three pharmaceutical companies.

The involvement of the UCL team under the supervision of Professor Timothy D. McHugh will assist the consortium in expertise on defining the mutation rates of the new lead molecules and on the genetic mapping of drug resistant phenotypes (Pope et al. 2008; O'Sullivan et al. 2010) by applying both established and new cutting-edge methodologies in genomics and transcriptomics. These technologies will enable us to define and characterise the mode of action of novel inhibitors, their possible role in the development of drug resistance and their associated fitness cost to the bacteria.

Contact for further information Prof Tim McHugh
Project website
http://www.predict-tb.eu/
Title

INFECT-MET: Metrology for monitoring infectious diseases, and harmful micro-organisms

Lead Dr Isobella Honeyborne
Participants Prof Tim McHugh, Dr Dimitrios Evangelopoulos
Funding Body EURAMET –EMRP
Project start/end dates 01/07/2012 – 01/04/2014
Description: 200 characters max.

INFECT-Met will investigate the development of higher order reference measurement methods and procedures. It will consider the process as a whole incorporating sample extraction and highly accurate and sensitive methods for enumerating single molecules and infectious particles and define the measurement capability of widely used and emerging molecular approaches. A measurement framework will be developed in close co-operation with key stakeholders including healthcare providers, public health laboratories, the academic research community, standards bodies, biotechnology and diagnostics Industries.

UCL is providing expertise in molecular diagnosis and monitoring of Mycobacterium tuberculosis to this project.

Contact for further information Dr Isobel Honeyborne
   
Title Differential effects of anti-TNF therapies for inflammatory arthritides on immune responses to Mycobacterium tuberculosis.
Lead Dr Rachel Byng-Maddick
Participants

Dr Mahdad Noursadeghi

Professor Mike Ehrenstein

Funding Body Arthritis Research UK
Project start/end dates 2012-2015
Description: 200 characters max.

Tumour necrosis factor (TNF) antagonists have revolutionised the therapy for rheumatoid arthritis and other inflammatory arthropathies. This success is partly tempered by the substantially increased risk of granulomatous infectious diseases, particularly tuberculosis (TB). My aim is to elucidate how TNF blockade leads to an increased incidence of tuberculosis. In those patients with inflammatory arthritis and known immunological memory for Mycobacterium tuberculosis (Mtb), a novel in vivo approach based on genome-wide transcription profiling of skin biopsy samples after intradermal injection of TB antigens will be used, to assess the effects of anti-TNF therapies at molecular and systems levels. Additional ex vivo and in vitro experiments, will be used to test the hypothesis that regulatory T cells, previously identified to be induced by anti-TNF antibodies, modulate innate (mononocyte, macrophage and dendritic cell) or adaptive (T cell) immune responses to Mtb. These results will inform the development of rational approaches to prevention/treatment of

TB in patients receiving anti-TNF therapy and may allow more targeted therapeutic immunomodulation for the treatment of inflammatory arthritis. Biomarkers or assays could be identified to assess the potential of novel biologic agents to cause clinically significant immunodeficiency.

Contact for further information r.byng-maddick@ucl.ac.uk
Title

Next Generation Tests for Latent TB

Lead Ibrahim Abubakar
Participants

Funding Body NIHR
Project start/end dates

2012 to 2017

Description: 200 characters max.

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Contact for further information

h.stagg@ucl.ac.uk

Current projects commenced before 2012

Title

Observational study to estimate the changes in the efficacy of BCG with time since vaccination

Lead Ibrahim Abubakar, Marc Lipman
Funding Body NIHR
Project start/end dates 2011 to 2014
Description: 200 characters max. Two analytic observational studies will be conducted comparing the frequency of the BCG vaccine in people in people with and without a history of illhealth. Both studies will evaluate how the effect of BCG vaccine changes with time since vaccination. The first study will examine children aged from 0-17 years, born when BCG can be given in infancy. The second study will examine an adult age range from 23 to 37 years and aged 13-years old when the pre-2005 school aged BCG programme existed
Contact for further information
Title The cost effectiveness of genetic markers for antibiotic resistance in tuberculosis
Lead Ibrahim Abubakar, Marc Lipman
Funding Body NIHR
Project start/end dates 2011 to 2013
Description: 200 characters max.

This study will investigate the clinical impact and cost effectiveness of the use of genetic markers for identifying multi- or extensively- drug resistant (M/XDR) tuberculosis (TB) using real patient data in the UK.

Contact for further information Mary.Cooke@ucl.ac.uk
Title

PREDICT Study

Lead Ibrahim Abubakar
Funding Body NIHR
Project start/end dates 2011 to 2015
Description: 200 characters max.

This study aims to determine which of the currently available tests for 'latent' tuberculosis (TB) infection best predicts the likelihood of subsequent development of active TB disease in groups of people at high risk of having been exposed to TB (contacts of active TB cases and migrants from high burden countries).

Title REMoxTB: Rapid evaluation of moxifloxacin for treatment of tuberculosis
Lead Prof Tim McHugh
Participants Dr Anna Bateson, Dr Mike Brown, Mr Robert Hunt, Dr Sara Murthy, Mrs Katie Smith
Funding Body EDCTP, Global Alliance for TB drug development
Project start/end dates 06/01/2004 – 01/01/2014
Description: 200 characters max.

REMoxTb is a randomised placebo – controlled double blind trial comparing two treatment shortening regimens with the standard regimen (two months ethambutol, isoniazid, rifampicin and pyrazinamide followed by four months isoniazid and rifampicin) namely 1) two months moxifloxacin, isoniazid, rifampicin and pyrazinamide followed by two months moxifloxacin, isoniazid and rifampicin and 2) two months ethambutol, moxifloxacin, rifampicin and pyrazinamide followed by two months moxifloxacin and rifampicin for the treatment of adults with pulmonary tuberculosis. Recruitment has completed with 1931 patients from 7 countries across Africa, India and SE Asia

UCL provides supervision of the laboratory, clinical and overall trial management.

Contact for further information Prof Tim McHugh

One of the Centre for Clinical Microbiology's biggest projects, PanACEA, The Pan African Consortium for the Evaluation of Antituberculosis Antibiotics, is an externally funded international collaborative project exploring new drugs that have the potential to shorten TB treatment.

Page last modified on 20 dec 12 10:25