A new framework may better characterise the early stages of tuberculosis (TB) and improve research and clinical care, an international team of researchers has said.
Turning against the current “active” or “latent” classification of TB, the International Consensus for Early TB (ICE-TB) group released a five-state system that distinguishes disease from infection, clinical versus subclinical states, and the degree of likely infectiousness.
Medpage Today reports that the framework includes four disease states, including clinical TB (with symptoms) and subclinical TB (without symptoms), each categorised as either infectious or non-infectious. The fifth state is TB infection that has not progressed to disease.
“The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease,” wrote Hanif Esmail, PhD, of University College London, and co-authors in their position paper, published in The Lancet Respiratory Medicine.
Esmail and colleagues noted that the simple binary view of latent infection and active disease had been key to case detection and standardised treatment of symptomatic individuals – preventing millions of TB deaths worldwide in the past few decades – but “it had less of an impact on transmission and disease incidence, possibly because millions of individuals with tuberculosis do not present to health facilities or receive care”.
The ICE-TB group stressed the need for improvement in diagnostic tools and for a TB framework to be flexible as new research emerges.
“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,” said Esmail.
“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.”
Keertan Dheda, MBBCh, PhD, of the London School of Hygiene and Tropical Medicine in England, and Giovanni Battista Migliori, MD, of Istituti Clinici Scientifici Maugeri IRCCS in Tradate, Italy, agreed that people with subclinical TB could “could probably receive shorter effective two-month treatment regimens”.
“The authors must be commended on tackling a difficult and controversial area, and choosing a classification that is workable in the real world, including tuberculosis-endemic countries,” the duo wrote in an invited editorial.
They did caution, however, that there is no established method for determining the level of infectiousness in subclinical TB.
Around the globe, TB is the leading cause of death from an infectious disease. The M. tuberculosis bacteria tend to attack the lungs, but other organs – kidney, spine, and brain, for example – may be affected.
A vaccine has been available for more than a century, and drug treatments for nearly that long. A minority of infected individuals will go on to develop symptomatic disease, the presentation of which varies widely and may not always include cough.
“This classification moves the field forward, as the framework can be validated and moves the research fraternity closer to standardised definitions that will facilitate research, assist diagnostic product development, and accelerate the development of new interventions,” wrote Dheda and Migliori.
“The suggested framework is sufficiently simple, which will be useful in the real world, covers all forms of active TB (including extra-pulmonary TB and TB in children), will probably advance active case-finding (largely based on the presence of signs and symptoms) and improve recording instances of subclinical TB in national tuberculosis registers (the recording of which is currently not accommodated).”
The arrival of ICE-TB may also have implications for ongoing TB vaccine development.
The ICE-TB framework was developed by an international, multidisciplinary group participating in two rounds of surveys. Participants represented the World Health Organisation (WHO) regions of Africa, the Americas and Europe, the Eastern Mediterranean, South-East Asia, and the Western Pacific, and more than half of the represented countries were low-income.
The 71-person group reached a final consensus on conceptual states, related terminology, and research gaps in TB during an in-person symposium in 2023.
“This new classification will provide a foundation for research and progress in diagnosis and treatment across the full spectrum of tuberculosis to reduce the global burden of morbidity and mortality,” wrote Lancet Respiratory Medicine journal staff in their own editorial.
Study details
Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise
Anna Coussens, Syed Zaidi, Glenda Gray, Mikashmi Kohli et al.
Published in The Lancet Respiratory Medicine on 22 March 2024
Summary
The current active–latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.
Medpage Today article – New Tuberculosis Framework May Improve Research, Clinical Care (Open access)
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