The new TB classification aims to improve focus on the early stages of the disease

A new way of classifying tuberculosis (TB) which aims to improve focus on the early stages of the disease has been presented by an international team involving researchers at UCL.

The new framework, published in The Lancet Respiratory Medicineseeks to replace the approach of the last half century of defining tuberculosis as either active (ie causing disease and potentially infectious to others) or latent (infection with the bacterium that causes tuberculosis [M tuberculosis] but we feel well and it’s not infectious to others) – an approach researchers say is limiting progress in eradicating the disease.

It is worth noting that large surveys recently carried out in more than 20 countries have shown that many people with infectious tuberculosis feel well.

Under the new classification, there are four disease states: clinical (with symptoms) and subclinical (without symptoms), each of which is classified as either infectious or non-infectious. The fifth state is M. tuberculosis infection that has not progressed to disease – that is, M tuberculosis it can be present in the body and alive, but there are no signs of the disease that can be seen with the naked eye, for example by imaging.

Researchers say they hope the International Consensus Framework for Early TB (ICE-TB), developed by a diverse group of 64 experts, will help better diagnose and treat the early stages of TB, which have historically been overlooked in research.

Tuberculosis currently remains the world’s deadliest infectious disease and has caused more than a billion deaths over the past 200 years. An estimated three million cases per year are not reported to health systems and more than half of these cases will be asymptomatic.

The international team was led by researchers at UCL, London School of Hygiene & Tropical Medicine, The Walter and Eliza Hall Institute (WEHI), University of Cape Town, Imperial College London and the South African Medical Research Council.

The binary paradigm of active disease versus latent infection has led to a one-size-fits-all antibiotic treatment for all diseases, but designed for those with the most severe form of disease. This leads to potential overtreatment of people with subclinical TB.

A key research priority now is to determine the best combination, dosage and duration of antibiotics to treat each TB condition, as well as the benefits of treating subclinical conditions.”

Dr Hanif Esmail, co-lead author at the UCL Institute for Global Health and MRC Clinical Trials Unit at UCL

Professor Rein Houben (London School of Hygiene and Tropical Medicine), co-leader of the work, said: “While providing treatment to people who become very ill with TB has saved millions of lives, we are not stopping the transmission of the disease.”

“To prevent the transmission of TB, we need to move away from focusing only on the very sick and look at previous states of disease, identifying people who may be infectious for months or years before developing TB symptoms.

“Our consensus framework replaces the old binary concept of ‘active’ versus ‘latent’ TB with a more detailed classification system that we hope, if widely adopted, could help improve treatment for people with early-stage TB and to advance efforts to eradicate the disease.”

The framework was developed through a Delphi process designed to achieve consensus among a diverse group. The process began with a scoping review of paper and electronic expert surveys and culminated in a two-day meeting in Cape Town, South Africa, of researchers from a range of disciplines, as well as policy makers, clinicians and TB survivors.

Dr Anna Coussens, co-lead author from WEHI, said: “A key finding in the consensus is moving the threshold of disease and recognizing that disease does not just start with symptoms or transmission, but when tissue is damaged.

“We hope that over time our framework can help eliminate TB by leading to improved early diagnosis and treatment, optimizing patient outcomes and minimizing transmission.”

The researchers observed that the disease process was non-linear – that people could fluctuate between infectious and non-infectious states and between the presence and absence of symptoms or signs.

They also said better diagnostic tools are needed to identify many of the TB conditions. For example, there is currently no test to detect a viable M tuberculosis infection (ie, where the bacteria are physiologically active), as opposed to a nonviable infection or a recent infection that has cleared.

The international team involved stakeholders from 19 countries, including the International Union Against TB and Lung Disease, The StopTB partnership, World Health Organization, FIND, National TB Programmes, TB Proof and researchers from various universities and medical research institutes.

The work was supported by Wellcome, the National Institutes of Health/RSA Report, the Bill and Melinda Gates Foundation, the Medical Research Council, the European Research Council and the National Health and Medical Research Council.