London School of Hygiene & Tropical Medicine

Tuberculosis (TB) should be a disease of the past, sadly it is very much a disease of the present. We’ve known about it since ancient times yet it is the leading cause of death through a single infectious disease in the world today, causing 1.5 million deaths every year. 

The World Health Organization has developed The End TB Strategy as a response to the global TB epidemic. The vision? Zero deaths, disease and suffering from TB by 2035. So how close are we to realising this vision? What steps need to be taken and why is TB so difficult to eradicate?

Without question the rise of multi-drug resistant tuberculosis (MDR-TB) is one of the most pressing public health challenges facing TB control today – nearly half a million cases of MDR-TB are diagnosed annually and this likely represents only the tip of the iceberg – most MDR-TB probably goes undiagnosed. Combatting MDR-TB requires robust information about the drug resistance profile of the strain involved in every case of TB, something we are lacking.

Diagnosis is also key. The earlier TB is spotted, the earlier life-saving treatment can begin. However, in some countries diagnostics have not changed for many years, with smear microscopy, chest x-ray and bacterial culture the mainstay of TB diagnosis. While recent advances in molecular diagnostics are changing the landscape for the diagnosis of TB, the accuracy of such tests in many subpopulations such as children is still poor.

Surprisingly, our knowledge of how Mycobacterium tuberculosis is transmitted remains limited, especially in areas where the disease is highly prevalent.  Improved tests for TB infection, cough studies, mathematical modelling and other crucial analytical tools remain few and far between.

We know that key drivers of TB transmission include HIV co-infection, increasing levels of other co-morbidities such as diabetes, poor housing and living standards and social deprivation. But the extent to which each of these factors determine the global trend is less clear.

An effective vaccine to protect against adult, pulmonary TB disease remains elusive. Such a vaccine is likely to be vital if we are to reduce transmission of TB and accelerate the current decline in global TB incidence.

So does the outlook for beating TB remain bleak? Well no – there is huge work to do but there is light at the end of the tunnel. Research featured in a new series in the journal BMC Medicine highlights that key advances are being made.

The introduction of molecular tools has facilitated a rapid, albeit imperfect, picture of drug resistance strains. Innovative technology such as molecular fingerprinting and geographical information has improved our understanding of several aspects of TB transmission over the last two decades.

Research is beginning to offer clues on transmission. In low incidence, high income countries, homelessness, drug misuse and imprisonment are now known to be major factors.

The increased availability of whole genome sequencing offers hope for improved diagnostics. It is also providing a greater insight into the genetics behind related strains and allowing the more efficient investigation of outbreaks.

A new tool for screening pre-clinical vaccine candidates has been developed, and we have identified new biomarkers for TB which have shown for the first time why immunity from the widely used Bacillus Calmette-Guérin vaccine is so variable. These will also provide valuable clues to assess whether potential new vaccines could be effective.

So where does that leave us? Well the theme of this year’s World TB Day is ‘Unite to end TB’ – and it is very apt. Only through a concerted, collaborative effort will we develop the improved diagnostics, treatments, vaccines and public health measures which are required.

Small steps in the fight against TB are being made – but these are is not enough. Only by accelerating the pace of research will we make the big strides required if we are to rid the world of TB by 2035.

Publication:

• The BMC Medicine Series includes research led by David Moore, Helen Fletcher, Taane Clark Richard White, Laura Rodrigues, Ankur Gupta-Wright, Stephen Lawn and Katherine Fielding

Image: Drug-resistant Mycobacterium tuberculosis. Credit: CDC/ James Archer