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Can we beat tuberculosis?

by Arundhati Maitra and Sanjib Bhakta | @Andebes | Thomson Reuters Foundation
Tuesday, 26 March 2013 19:00 GMT

* Any views expressed in this opinion piece are those of the author and not of Thomson Reuters Foundation.

With millions of TB cases reported each year, this question poses one of the most serious challenges for the scientific community

The following blog is written by Arundhati Maitra and Sanjib Bhakta of the Department of Biological Sciences, Birkbeck, University of London

With an estimated 8.7 million reported cases and 1.4 million deaths due to TB in 2011, the question above poses one of the most serious challenges faced by the scientific community, healthcare industry, government and public organisations worldwide.

However, this year on World TB Day whilst commemorating Dr Robert Koch’s discovery of the germ (Mycobacterium tuberculosis) causing tuberculosis back in 1882, we can share many positive signs. 

Following the discovery of the agent causing TB came the golden era of antibiotic discovery spurred on by the serendipitous discovery of penicillin by Alexander Fleming. Streptomycin, the first known cure for TB was hailed as a success and led to the belief that the disease was close to being eradicated. Soon after, resistant forms of the bacillus showed up. To tackle resistance a lengthy multidrug regimen was proposed. However, non-adherence to treatment has allowed the rise of extensively- and even total-drug resistant (XDR/TDR) forms of the bacteria. As their name suggests, there are virtually no drugs available to effectively treat a patient infected with XDR/TDR-TB.

What makes these bacteria so successful in causing infection? Firstly, they are equipped with complex tools that enable them to evade the infected patient’s immune responses. Secondly, their cell wall serves as a barrier to most drugs. The bacteria can also lie dormant for years inside the host tissues and ‘wake up’ to cause full-blown infection. TB is especially fatal in individuals with compromised immunity due to aging, malnutrition, HIV co-infection, cancer, smoking or even high blood sugar.

Detection of the disease still poses problems today, as the highest incidence rates of TB are in economically challenged areas that lack the necessary infrastructure for fast and accurate point of care detection of TB. Due to the slow growing nature of the bacteria, culture tests require a minimum of two weeks before results can be ascertained. Tests to detect drug resistance might take longer.

These obstacles, though formidable, are not insurmountable. New diagnostic tools that are both speedy and accurate are already in use today (Xpert MTB/RIF, IGRA tests) and many more are in the pipeline.

Novel anti-tubercular drug regimen that shorten treatment period is the need of the hour. It calls for further research to determine targets essential for the bacteria to survive inside the host environment. A key constituent of the cell wall of Mycobacterium tuberculosis - the peptidoglycan layer, has garnered a lot of attention recently, as it could provide molecular network specific to the bacteria that can be targeted against.

Once obtained, these anti-tubercular molecules require rapid screening techniques to determine their potency against the bacteria. One such reliable and reproducible gold standard method called the HT-SPOTi assay has been developed at the ISMB mycobacteria research lab at Birkbeck, University of London. By using this assay, we found a selection of inexpensive and safer over the counter drugs to show anti-TB activity against both dormant and active MDR-TB germs isolated from patients. 

Parallel to this study Ben Gold et al elegantly demonstrated another non-steroidal anti-inflammatory drug (Oxyphenbutazone) to have similar anti-TB properties. Such repurposing of existing drugs could potentially save time and mammoth investments required for a new antibiotic development programmes. Developing new regimens with existing anti-TB drugs and new candidate drugs, some of which are in the various phases of current clinical trials, could offer a brighter future for the shortening of treatment of this disease.

Another approach required is in the field of vaccine development. The current vaccine against TB, the BCG vaccine, offers partial protection to infants. WHO reports around 11 vaccines are presently in clinical trials. A more robust vaccine would cause a drastic reduction in the number of incidences of the disease.

A steady fall in new incidences and mortality caused by drug-susceptible forms of TB has already been observed. A focussed approach towards tackling the drug-resistant forms of the disease and its synergistic association with HIV should enable us to reduce the threat of this highly infectious disease on the well-being of mankind. 

(Arundhati Maitra is an associate research fellow and Sanjib Bhakta is academic head and director of ISMB-Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London and Research Department of Structural and Molecular Biology, UCL) 

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