Questioning the Epidemiology of Subclinical Tuberculosis

Introduction

Tuberculosis (TB) remains a major cause of morbidity and mortality around the world. The majority of TB control policies rely on the binary paradigm of TB, which focuses on interventions tackling ‘latent’ TB infection and ‘active’ TB disease stages.

Evidence of Continuous Spectrum

However, recent evidence disputes this longstanding conceptualization of TB natural history, demonstrating that TB exists on a continuous spectrum of bacterial and immunological responses. Several active case-finding studies have shown that around 50% of the cases in whom Mycobacterium tuberculosis was isolated in sputum were asymptomatic.

Importance of Subclinical TB

Subclinical (asymptomatic) TB has lately attracted increased scientific interest since it could play an important role in TB transmission, despite the absence of cough. However, beyond limited evidence on TB transmission based on modelling studies using retrospective data collection, there is not a single field study showing a direct transmission from an index subclinical TB case to a secondary laboratory-confirmed case.

Implications for Global TB Control

If subclinical TB does spread the disease, the consequences for global TB control and research are of paramount importance. I propose to characterize the subclinical TB stage within the natural history of TB and to understand its role in spreading the disease.

Study Design: TB-QUEST

I have designed a field epidemiological study (TB-QUEST) with the potential to show evidence of effective transmission from subclinical TB cases to close contacts, using pathogen genome sequencing.

Innovative Technology

Additionally, by using innovative wearable technology, I will assess whether objective tools to measure classical TB symptoms match the self-reported absence of symptoms. Thus, I might challenge the current definition of subclinical TB and the usefulness of current TB screening algorithms.

Clinical Trajectory of Subclinical TB

Lastly, I will study the clinical trajectory of subclinical TB in order to improve our understanding of its natural history, duration of infectiousness, and factors associated with self-clearance or progression to symptomatic disease.