An observational study in Tuberculosis, Tuberculosis (TB) and HIV, sponsored by Barcelona Institute for Global Health. Recruiting at 1 site in Mozambique. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-31.
Sponsored by Barcelona Institute for Global Health · Observational
Tuberculosis (TB) remains one of the world's leading causes of morbidity and mortality. Current TB control strategies focus largely on the binary paradigm of TB, which tackle Mtb infection and the symptomatic stages of the disease as the major drivers of the TB epidemic. However, prevalence surveys have shown that about 50% of cases in which Mycobacterium tuberculosis is isolated from sputum but do not report having symptoms. Therefore, asymptomatic TB may play an important role in TB transmission. However, no field study has demonstrated direct transmission from a subclinical TB case to a confirmed secondary case.
TB-QUEST is an ERC-funded epidemiological field study that aims to provide direct evidence of effective transmission from asymptomatic TB cases to their close contacts using advanced genomic methods, and to better characterize the asymptomatic stage of TB within the natural history of disease.
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%.
TB QUEST will conduct an initial cross-sectional assessment among PLHIV attending routine follow up visits in order to identify bacteriologically-confirmed asymptomatic and symptomatic TB cases. It follows with a nested prospective contact cohort study in which two cohorts of close-contacts exposed to the aTB and clinical TB cases, respectively, will be followed up periodically for 12 months. The project embeds three additional longitudinal assessments: a) one among both asymptomatic and symptomatic TB cases to objectively verify the presence of common TB symptoms, b) one among a proportion of aTB cases that will be closely monitored for radiological, microbiological and clinical changes to assess the trajectory of aTB, and c) one in which a subset of non-infectious aTB patients will be followed to observe its trajectory.
TB-QUEST will generate high-quality evidence to resolve the current hypotheses on aTB transmission. If aTB plays and important role in TB transmission, the current pillars of TB control will prove to be insufficient to achieve the reduction of TB incidence and mortality set by the international community. Thus, this proposal has the potential to represent a paradigm shift for TB control. The evidence derived from this study will challenge global symptom-driven case finding strategies, as well as the clinical management of aTB cases. Further, disentangling the evolution of aTB may allow for its inclusion as a primary endpoint in TB vaccine and drug trials, improving efficiency in future TB research and the development of new tools to fight the disease.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's planned enrollment of 6,770 is above the median of 253 across 317 observational studies indexed under Tuberculosis.
Browse Tuberculosis studies →Barcelona Institute for Global Health is the lead sponsor of 24 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Participants attending routine HIV care at the Manhica District Hospital
Index cases:
Inclusion Criteria:
Exclusion Criteria:
Study 3 will utilize additional inclusion criteria:
Inclusion criteria:
Contacts:
Inclusion criteria: All close contacts (household and close community contacts) will be offered to participate in the study, regardless of age or HIV status.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contacts of bacteriologically-confirmed asymptomatic TB index cases
Contacts of bacteriologically-confirmed symptomatic TB index cases
Proportion of secondary cases arising from TB index case transmission
Transmission from aTB cases will be compared to that of clinical cases by: i) comparing the proportion of genomically-linked secondary cases and ii) by comparing the proportion of QFT conversion and host transcriptomic changes
Time frame: 12 months
Symptomatology of asymptomatic TB
The objectively measured frequency of symptoms among asymptomatic TB cases compared to that of symptomatic TB cases
Time frame: 2 weeks
Clinical trajectory of aTB
The proportion of aTB cases with measurable signs of progression to symptomatic or worsening TB disease compared to those who self-clear.
Time frame: 12 months
Plan to share: Undecided
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Barcelona Institute for Global Health