New classification of tuberculosis to support efforts to eliminate the disease

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.

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

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

“To prevent transmission of TB, we need to move away from focusing just on the very sick and look at earlier disease states, identifying people who may be infectious for months or years before they develop 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 to improve treatment for those with early-stage TB and drive forward efforts to eradicate the disease.”

The framework was developed via a Delphi process designed to reach a consensus among a diverse group. The process began with a scoping review of papers and online surveys of experts and culminated in a two-day meeting in Cape Town, South Africa, of researchers from a range of disciplines as well as policymakers, clinicians, and TB survivors.

Dr. Anna Coussens, co-lead author from WEHI, said, “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.

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

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

They also said 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 (i.e., one where the bacteria are physiologically active), as opposed to a non-viable infection or recent infection that has cleared.

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