New insights into mechanics of TB transmission brings control closer
Around 10 million people get seriously ill with tuberculosis (TB) every year, and even though we have effective treatment, over 1 million die from the condition, according to the World Health Organization. “On top of those 10 million, we now know TB causes some damage to people’s lungs or other organs in millions more, yet global policy mostly ignores these groups,” says Rein Houben, co-leader of the TB modelling group at the London School of Hygiene and Tropical Medicine. Although there has been a slow fall in the numbers of those infected, of around 2 % a year, it is much less than needed if we are to reach the World Health Organization’s Sustainable Development Goals, which set a target of a 90 % reduction in the number of TB deaths and an 80 % reduction in the TB incidence rate, by 2030. “The fall is not just slow, it is also much less than expected, given how many people are being treated for TB, which should have led to more rapid reductions. But this gap between expectations and reality is partly what our work looked to explain,” remarks Houben, coordinator of the TBornotTB project, which was funded by the European Research Council (ERC).
Questioning the established paradigm of TB infection
At the start of the TBornotTB project there were already signs that established truths did not hold. A cornerstone of TB policy had been the classic paradigm that those who were ill and could transmit TB would have symptoms and go to a clinic. Treatment would then save their lives and protect the community. However, that link between symptoms and transmission is not true, “Which,” says Houben, “is a big problem, with many consequences.” He thinks that belief in the classic paradigm is now mostly gone, in part thanks to the findings of the project. Like almost everybody in the past four decades, Houben was taught that someone either had a ‘latent infection’ in which case there was no illness and no treatment required. Alternatively, the disease was ‘active’, meaning symptomatic, infectious and where patients had a high risk of death unless treated. “It was thought that there were no ‘in-between’ states and that TB, if it hit you, hit instantly and hit hard,” he adds. But when healthcare providers started asking people who had TB whether they were aware of any symptoms, around 50 % said no. So the project turned to historical records from 1905 to the 1960s, during which time there was no treatment, and contemporary data, to try and establish the missing part of the puzzle. “While tragic for the many people who suffered from TB without treatment, these old data could tell us how TB developed over time, how many people recovered, and how fast,” he explains. The contemporary data were from prevalence surveys: massive studies in which tens of thousands of people are screened for TB, which show how big the TB iceberg really is and how much subclinical transmission was going on.
Surprising findings reveal shortcomings of TB policies
“Those data showed us that almost everything we were taught about TB was wrong. There are not two states, with a single step change between them. TB in humans causes damage across a wide spectrum of disease, and people can and do move up and down this spectrum. The consequence is that current TB policies are almost certainly wildly insufficient to actually stop TB causing untold damage to individuals and their communities,” Houben says. This spectrum of disease was well known between 1900 and 1960, but, Houben explains, simply vanished from TB teaching and policy. “We are now rediscovering knowledge that existed before.” These vital insights, he feels, are a result of a growing group of scientists questioning the status quo. “Thankfully the ERC was willing to fund our team to work through piles of old papers in three languages, to find and then use the data reported within,” he notes.
Putting new understanding into practice when it comes to TB management
As the team was venturing in unknown scientific territory, it took time to find solid ground, and longer than expected to get all the data and the model together. But now that they have developed the model, they can address big policy questions. In particular, how different diagnostic strategies perform when the disease is considered as a spectrum, rather than the single disease state as before. “One key finding,” adds Houben, “is that current TB policies, even if they perform at 100 % (which they never do), will miss more than half of all transmission. If we don’t change, we will not end TB in our lifetime. Indeed, it is uncertain if we ever can, without rethinking our preconceptions.”
Keywords
TBornotTB, ERC, TB, tuberculosis, TB infection, transmission, policy
