The future of TB diagnosis: the paradigm shift?

July 15, 2011

Posted by The KC team

The Alliance hosts a citizen journalism programme called Key Correspondents (KCs).

By Key Correspondent Prakash Tyagi

Over a hundred years into the current fight against tuberculosis (TB), it remains one of the world’s most critical medical and public health challenges. Not only has the disease steadily caused a great deal of illness and death over the years, tackling it has become more complex and difficult.

It is estimated that around nine million new cases emerge and two million people die from the disease every year. One third of the world’s population is infected with M. Tuberculosis (MTB), a latent form of TB, which will become active in 10 per cent of us.

The numbers are significant in developing parts of the world – Asia and Africa for example – and the gap is widening between Eastern and Western parts of Europe. The epidemiological evidence is sound – the global fight against TB remains impacted by varying developmental standards and unequal achievements.

To understand why TB remains such a threat to public health we must understand some of its complexities, starting with the changing trends behind diagnostic approaches.

Most of the current diagnosis is currently done through techniques such as the Tuberculin Skin Test (TST), and via chest x-ray. But the TST is proving to be largely ineffective as it can give a false negative result, especially in patients infected with other conditions such as sarcoidosis (which can cause inflammation of the lungs). It can also give a false positive in children who have received the BCG vaccine, which immunizes against TB. A limitation is that it is unable to differentiate MTB from other stains of TB, especially with NTM (Non Tuberculous Mycobateria). T-cell related assays (procedures) known as IGRAs are commonly used too, with certain advantages and disadvantages.

A second critical complexity stems from the growing problem of Drug Resistant TB (DR TB). What’s worse, the ratios of Multiple Drug Resistant TB (MDR TB) and Second Line Drug Resistant or Extensive Drug Resistance TB (XDR TB) are on the rise. There is also good evidence of transmission of DR TB leading to primary drug resistance.

The other form of resistance – acquired drug resistance – is mainly witnessed as a result of non-compliance with TB treatment, poor quality drugs or poorly organized therapy (including monotherapry). With 440,000 cases of DR TB in the year 2008, and 150,000 deaths in the same year, the resistance issue is certainly at the forefront of TB control strategies. The long gap in researching new medicines, it could also be argued, means it has been a while since the last regimen came into existence.

Finally, there are the all important factors relating to other infections, known as co-infection or co-morbidity. The evidence is loud and clear that tubercular infection is associated with a number of life-threatening conditions, making diagnosis and treatment challenging. The HIV-TB co-existence barely needs mentioning, so much has it been talked about. Some of the other, under-estimated challenges come when someone has both pneumoconiosis and TB, has Chronic Obstructive Pulmonary Disease (COPD) or has been exposed to bio-mass fuel pollution.

Various forms of pneumoconiosis (silicosis, coal workers’ lungs) remain critical challenges in many countries. COPD is predicted to be the third largest killer by 2030 and often coexists with TB. By 2030, a staggering 210 million globally will be living with COPD and it will be the seventh largest contributor to disability adjusted life years (DALYs) calculations, which counts the years of potential life lost due to premature illness and the years of productive life lost due to disability.

TB remains vastly under diagnosed. In order to treat TB effectively, it needs to be identified with a greater degree of accuracy.

Molecular diagnosis is the latest area of research in TB diagnosis – tests such as Genotype MTBC and LAMP. Researchers believe these tests are more accurate, detect the disease early and reduce secondary resistance. Their effectiveness in DR TB is also an advantage. Nevertheless, there is a flip side. The technology is expensive, has a lower sensitivity in smear-negative cultures and requires DNA extraction. To take this further to the communities which are largely impoverished is a difficult preposition.

Thus, the paradigm shift in diagnosing TB will need to consider the practical difficulties in implementation and outreach.

In the global fight against TB, let us not be naive and complacent. Let us be realistic and exploratory.

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