A new classification of tuberculosis could support efforts to eliminate the disease. 

Experts have published a new framework that seeks to replace the approach of the last half century of defining TB as either active (causing illness and potentially infectious to others) or latent (being infected with the bacterium that causes TB [M. tuberculosis] but well and not infectious to others).

Researchers say this approach is limiting progress in eradicating the disease. The simplest evidence comes from large surveys conducted in over 20 countries, which show that many people with infectious TB report feeling well.

Under the new classification, there are four disease states: clinical (with symptoms) and subclinical (without symptoms), with each of these classed as either infectious or non-infectious.

The fifth state is M. tuberculosis infection that has not progressed to disease – that is, M. tuberculosis may be present in the body and alive, but there are no signs of the disease that are visible to the naked eye, for example with imaging.

The researchers say they hope the International Consensus for Early TB (ICE-TB) framework, developed by a diverse group of 64 experts, will help lead to better diagnosis and treatment of the early stages of TB which have historically been overlooked in research.

TB remains the world’s most deadly infectious disease and has caused over one billion deaths in the last 200 years. 

An estimated three million cases a year are not reported to health systems and more than half of these cases will be asymptomatic.

“One key finding in the consensus is moving the disease threshold and acknowledging that disease does not just start with symptoms or transmission, but when tissue is damaged,” says WEHI Lab Head and paper co-lead author Dr Anna Coussens.

“In time we hope our framework can contribute to TB elimination by leading to improved early diagnosis and treatment, optimising patient outcomes and minimising transmission.”

The researchers noted that the disease process is non-linear - people may fluctuate between infectious and non-infectious states, and between the presence and absence of symptoms or signs.

They also say that better diagnostic tools were needed to identify many of the TB states. 

For instance, there is currently no test to detect a viable M. tuberculosis infection (one where the bacteria are physiologically active), as opposed to a non-viable infection or recent infection that has cleared.

“The binary paradigm of active disease versus latent infection has resulted in a one-size-fits-all antibiotic treatment for disease, but designed for those with the most severe form of disease,” says Dr Hanif Esmail, co-lead author from University College London.

“This leads to potential over-treatment of individuals with subclinical TB.

“A key research priority now is to identify the best combination, dosage and duration of antibiotics to treat each TB state, as well as the benefits of treating the subclinical states.”