Beyond latent and active – a scoping review of conceptual frameworks and diagnostic criteria for tuberculosis
Authors: Zaidi Syed MA , Coussens Anna K , Seddon James A , Kredo Tamara , Warner Digby , Houben Rein M G J , Esmail Hanif 
Published: July 2023

AbstractBackgroundThere is growing recognition that tuberculosis (TB) infection and disease exists as a spectrum of states beyond the current binary classification of latent and active TB. Our aim was to systematically map and synthesize published conceptual frameworks for different TB states from the literature.MethodsWe searched MEDLINE, Embase and EMcare for systematic and narrative reviews without date restrictions. We included articles that explicitly described greater than two states for TB. We conducted a thematic and frequency analysis for terminologies, conceptual definitions and diagnostic criteria for defined TB states.ResultsWe identified 37 articles that met our inclusion criteria. All included articles were published after 2009. We identified eight broad conceptual themes that were used to categorize TB states and to calculate their frequency among included articles. These states were: State 0:Mycobacterium tuberculosis(Mtb) elimination by innate immune response (n=23/37, 62%); State I:Mtbelimination by acquired immune response (n=28/37, 76%); State II:Mtbinfection not eliminated but controlled by immune system (n=34/37, 92%); State III:Mtbinfection not controlled by the immune system (n=21/37, 57%); State IV: bacteriologically positive without symptoms (n=23/37, 62%); State V: signs or symptoms associated with TB (n=36/37, 97%); State VI: severe or disseminated TB disease (n=11/37, 30%); and State VII: previous history of TB (n=5/37, 14%). We found 27 additional variations within these themes that were labelled as “sub-states.” Articles varied in the terminology used to describe conceptual states and similar terms were often used to describe different concepts. Diagnostic criteria were provided in 27 articles and were also applied inconsistently.ConclusionTerminologies and definitions for TB states are highly inconsistent in the literature. Consensus on a framework that includes additional TB states is required to standardize communication in scientific publications as well as to inform advancements in research, clinical and public health practice.Panel: Research in contextEvidence before this studyThe current paradigm of tuberculosis (TB) is based on a binary classification into “latent” infection and “active” disease states. In recent years, there has been growing recognition that this binary classification does not accurately reflect the complex pathophysiology of the disease process and that it may also be inadequate for informing research and programmatic advances for global TB elimination. While a number of articles have proposed multiple states of infection and disease, no previous study has mapped and synthesized evidence from published literature to inform an overarching and inclusive staging framework. We conducted a comprehensive search on MEDLINE, Embase and EMCare databases for systematic or narrative review articles or commentaries with terms related to TB and “states”, “stages,” “paradigm” “framework” or “spectrum” without date restrictions. We included 37 articles that explicitly described TB as a multi-state, i.e., beyond latent and active disease.Added value of this studyTo our knowledge, this is the first study to systematically review conceptual frameworks, terminologies and diagnostic criteria for TB states beyond the latent and active paradigm. We identified that there is substantial variation in the number of TB states described in the literature, as well as in the concepts used to categorize them. Terms used for describing TB states and their diagnostic criteria were also inconsistently applied.Implications of all the available evidenceOur review highlights the need for a clear consensus on the overall conceptual framework, terminology and diagnostic criteria for TB states. The inconsistency in TB states among articles included in our review reflects diverse perspectives, academic interests and research priorities. The consensus process should therefore aim to be inclusive so that a proposed framework can be acceptable to a broad range of stakeholders including clinicians, researchers, public health and policy practitioners, as well as to individuals living with or with experience of TB.