Not only one leader, but many: Dr James Seddon calls for action on World TB Day

World TB Day, which falls on March 24th each year, is organised by the World Health Organisation with the aim to raise public awareness of the devastating consequences of tuberculosis (TB) and the on-going efforts to end the global TB epidemic. To mark the occasion, we have discussed TB with Dr James Seddon, who has published a highly-accessed review about drug-resistant TB and advances in the treatment of childhood TB in our journal Pneumonia.

Dr James Seddon

24th March marks the day when Robert Koch discovered the infectious nature of TB and identified Mycobacterium tuberculosis as the bacterium responsible for this disease, paving the way for the development of diagnosis and treatment of TB.

Significant progress has been made in the curing TB and 53 million lives were saved through effective diagnosis and treatment of TB between 2000 and 2016, according to the WHO. However, TB is still far from being eradicated and the endemic of drug-resistant TB now poses a serious threat. The WHO estimates 490,000 cases of drug-resistant TB in the world in 2016 alone.

Can you tell me a bit about what you are working on at moment?

I am a paediatric infectious disease doctor splitting my time between London, where I spend one month a year working as a paediatric infectious diseases doctor, and Cape Town, where I do research. My focus is on implementing strategies to diagnose children with drug-resistant TB more easily and find better ways of treating them. I am currently working on study that will hopefully help identify which Tb-exposed are likely to develop disease in the future so that preventive therapy can be better targeted.

We are aiming to do this by identifying what genes are switched on or off following exposure to TB – we test the blood transcriptome of children to see what genes are activated and follow our patients for 2 years afterwards. Most of the children will not get TB following exposure to the disease, but a small percentage of children do. By comparing the transcriptomic profile of the two groups we hope to identify what genes are activated in children who later develop TB and use this profile to effectively start preventive therapy. In addition to this, I am working on amathematical modelling project to estimate the global impact of household contact activates to prevent TB disease and death in children.

What improvements have been made in the diagnosis and treatment of TB over the last few years?

Unfortunately the standard treatment for TB has been the same all over the world for years. However, there is now finally some activity. A new randomised trial called SHINE is looking to shorten standard treatment for children with drug-susceptible TB from 6 to 4 months. In addition there is some cause for optimism as two new drugs have recently been developed that could be used in drug-resistant TB, bedaquiline and delamanid. These drugs are currently only used in adults, as no safety studies have been conducted to assess their suitability in children.

However, a new trial, SMaRT Kids is in advance stages of planning and would aim to investigate the treatment of children with drug-resistant TB. The intervention arm would avoid using daily injections, as they are toxic and can cause deafness, and also reduce the duration of treatment to 6 months.

As for the diagnosis, there are really two main approaches. First, you can look for the organism. This can be through laboratory culture or DNA amplification. However, this can be challenging for children who often have more limited disease with fewer organisms and who also struggle to produce a sputum sample. The other approach is to evaluate the host response to the organism using host immunological diagnostics.

The theme for World TB day this year is “Wanted; leaders for a TB free world”, who do you see as leader in ending TB?

I do not think there needs to be only one leader, but many.

I do not think there needs to be only one leader, but many. We need political leadership, and this year, Heads of State will meet in New York at the United Nations General Assembly for a high-level meeting on TB for the first time ever. We need leadership at the level of global institutions, through the involvement of WHO, UNICEF and others. We need leadership at an academic level, with universities exploring new discoveries that will improve treatment. We need leadership in national healthcare departments and tuberculosis programmes and we need clinicians to step up and advocate for their patients. Finally, patients need to show more leadership in demanding better care. We all have a responsibility to support them.

What are the barriers in place that leaders will have to overcome to create a TB-free world?

Some of the barriers are biological as TB has evolved over millennia to evade our immune systems. There are also significant social barriers as TB generally affects the poorest and most marginalised groups in the most poor and marginalised countries. Some of the barriers are linked to the way TB has been perceived for a long time. Traditionally patients with TB were treated because the disease could spread to others – posing a public health threat. This has led to a very paternalistic way of treating patients, and we need to break this philosophy, empower patients and treat them with more respect.

Patients themselves have to take ownership in the way they are treated and make themselves heard. Everyone should get angry that there are still no solutions to this disease. Additionally, TB does not receive enough funding compared to other infectious diseases (HIV receives far more funding for research and development), but if there were louder active advocacy groups and more vocal politicians getting behind this then higher funding might be allocated to TB”.

Want to read more about childhood TB? Pneumonia has a whole thematic series on challenges and progress in childhood TB, and if you actively work in the field of TB the thematic series is still open for submissions.

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