This post was contributed by Arundhati Maitra, an associate research fellow, Department of Biological Sciences
World TB Day on 24 March marks the day in 1882 when Robert Koch discovered Mycobacterium tuberculosis, the causative agent of one of the most dreadful infectious diseases known to man – tuberculosis (TB). This year, on 21 March, Dr Sanjib Bhakta (Academic Head and Director of the Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Birkbeck) chaired a conference organised by EuroSciCon which raised the question – ‘Mycobacterium tuberculosis…Can we beat it?’ The event at The Royal College of Pathologists brought together several great minds in the field of TB research in the UK and from around the world.
The conference began with an introduction to the raging issues in TB management. Dr Bhakta emphasised the fact that an integrative approach is essential to target the various physiological states the germ can exist in inside an infected patient: active state, causing full blown infection, and the latent state, also called persisters, lying dormant within the patient.
In 1993, WHO reported TB as a global health emergency. The disease continues to remain a serious threat to mankind 20 years on. Though the TB incidence rates remain constant in the Eurozone, rates in the cosmopolitan cities in the UK such as London, Manchester, etc. speak of a different story. In 2011 the number of TB cases reported in London was higher than that of reported AIDS cases.
In a hard-hitting presentation, Professor Graham Bothamley of Homerton University Hospital, UK, remarked that the failure to contain the disease is largely due to the lack of political commitment and roadblocks in health care delivery. A survey across Europe showed that not only are drugs unavailable in some regions, but the regimens followed in various countries do not follow the tested, WHO approved guidelines, putting many lives at risk.
The essential requirements to lessen the burden of TB are twofold – speedy and accurate diagnostics and development of novel drugs and treatment regimens.
Diagnosis by sputum microscopy and culture tests are the predominant methods of TB detection. Professor Mike Barer from the University of Leicester reported an interesting finding which could have far reaching effects in latent TB detection. His group has recently discovered that sputum analysis, usually used to detect active infection could also give an insight to the level of persister population in the patient by detecting presence of lipid bodies in the bacteria.
Though remarkable, this still doesn’t answer the need for a rapid and accurate means of TB detection. That is what Christopher Granger, Director of Oxford Immunotech Ltd claimed to have achieved. He described the T Spot TB test, a simple test based on ELISpot assay, which is more specific than the regular tuberculin skin test, detects latent infection and is time as well as cost-effective. However, Dr Jayne Sutherland from the MRC Unit in Gambia mentions that a simple dip-stick test that can be available at the point-of-care is essential in the areas with highest incidences of TB. She described how many of the clinics are in remote areas and can only be referred to as ‘bush clinics’, lacking necessary infrastructure for TB detection. Her team is engaged in developing lateral flow based tests, something similar to the pregnancy test kits available today.
New diagnostic equipment to detect TB is being developed at the University of Amsterdam by Ngoc Dang. It detects biomarkers of lipid origins by thermally assisted hydrolysis and methylation followed by gas chromatography and mass spectroscopy. This equipment, when available, would have positive implications in areas where a large number of samples need to be tested.
Moving on to drug development and treatment strategies, Professor Stephen Gillespie of the University of St Andrews discussed several new anti-tubercular drugs and shorter treatment regimens in various phases of clinical trials. He also emphasised the need to develop predictive models for regimens as newer drugs are being discovered.
Detection of targets specific to the infectious agent is essential for the development of novel drugs. A couple of these targets were discussed by Dr Luke Alderwick from Birmingham University and Professor Edith Sim from Kingston University. While Dr Alderwick focussed on a cell wall synthesising enzyme, DprE1 and its inhibitor benzothiazinone (BTZ), Dr Sim focussed on enzymes essential for the bacteria’s survival within host cells, N-acteyl transferase and HsaD. Dr Brian Henderson from UCL described the role of proteins that have more than one specific function (moonlighting proteins) in virulence of these bacteria and suggested that these could be potential targets.
A common theme was observed in presentations by Dr Anthony R.M. and Professor Tim Mc Hugh. Both were strong proponents for the need to monitor the progress of treatment in the earlier stages rather than the current practice of 18 months on. The former explained a ‘treat to test’ strategy following the belief that upon starting of treatment an initial burst of dead cells makes for easy detection of the kinetics of the response of the host to treatment. The latter suggested the use of various biomarkers obtained from the bacteria and the host such as colony counts to assess bacterial load, bacterial RNA and small RNA from the host, to indicate the effectiveness of the treatment and likelihood of a relapse.
An interesting Q&A session began with a question regarding the importance of point-of-care diagnostics and was led by Dr Bhakta to touch on the other issues plaguing TB management today. Dr Juan D Guzman from ISMB, Birkbeck was asked to comment on the scaffolds found in natural and synthetic compounds that are especially effective as anti-tubercular drugs.
Poster presentations were invited and the top prizes went to Ngoc Dang, University of Amsterdam for her work on TB diagnostics and Dr Tulika Munshi from ISMB, Birkbeck, for her poster on ATP-dependant Mur ligases as novel therapeutic targets for TB drug development (http://dx.plos.org/10.1371/journal.pone.0060143).
On the whole, the conference was one step towards defeating TB as interdisciplinary research, collaborations and alliances are urgently required to fight this menace.
