Questioning the Epidemiology of Asymptomatic TB

The majority of TB control policies rely on the binary paradigm of 'latent' and 'active' TB. Recent research demonstrates that TB exists on a continuous spectrum of bacterial and immunological responses, and sheds light on the non-linear path that TB may take to advance or regress along the spectrum of disease. This understanding has led to the distinction between latent (M.tb infection), asymptomatic, and active (symptomatic) TB stages. Asymptomatic TB (aTB) stages have attracted increased scientific interest since they could play an important role in TB transmission. If this were the case, the implications for global TB control and research would be enormous. Thus, there is an urgent need for intensified research into this TB stage to better understand its public health importance and implications on TB transmission.

TB QUEST is a prospective epidemiological field study designed to address several critical research gaps surrounding aTB. The overall aim of the study is to provide direct evidence of asymptomatic TB transmission, and to better characterize the asymptomatic TB stage within the natural history of disease. This project has four main objectives:

Objective 1: To provide direct evidence on the successful transmission of tuberculosis infection (leading to TB disease) by individuals diagnosed with aTB Objective 2: To ascertain the presence of typical TB symptoms in self-reported asymptomatic laboratory-confirmed TB patients Objective 3: To understand the factors associated with Mtb self-clearance or disease progression in patients with aTB Objective 4: To understand the characteristics and progression of non-infectious aTB

TB QUEST will recruit asymptomatic and symptomatic index TB cases as well as their close contacts, allowing for the observation of secondary (genomically-linked) cases and new infections while providing direct temporal characterization and directionality of TB transmission. In addition, TB QUEST nests three additional longitudinal assessments among individuals with aTB in order to ascertain presence of symptoms and assess their clinical trajectory.

The project is coordinated by the Barcelona Institute for Global Health (ISGlobal) in close collaboration with the Centro de Investigação em Saúde de Manhiça (CISM), located in the district of Manhiça, Mozambique, where all field work will be conducted. The district of Manhiça is a high TB/HIV burden area in Southern Mozambique, where the latest reported TB case notification is around 500 per 100,000 population and the prevalence of HIV in the adult population was 35%.