Detection of Mycobacterium Tuberculosis in Blood of TB Patients and Their Contacts in Uganda

Mycobacterium tuberculosis (Mtb) is a major human pathogen, responsible for an estimated 10.6 million cases of active tuberculosis (TB) and 1.6 million deaths in 2021. Most adult cases of active TB arise from progression of latent tuberculosis infection (LTBI), whose global prevalence is estimated at 23%. Preventive therapy (e.g. a 6-month course of the anti-TB drug isoniazid) is effective in reducing risk of progression from LTBI to active TB. Global roll-out of preventive therapy will be required to achieve the World Health Organization target of TB elimination by 2050, but this will only be cost-effective and implementable if targeted at the 10-20% of latently infected individuals who are at highest risk of disease progression. There is currently no gold standard test for LTBI. Existing diagnostic - the tuberculin skin test (TST) and Interferon-γ Release Assays (IGRA) - diagnose Mtb infection by detecting memory T cell responses to Mtb antigens. Their value is limited by very low positive predictive value (PPV) for progression to active TB (1.5% for TST, 2.7% for IGRA), inability to detect antimicrobial resistance in latently infected individuals and lack of response to administration of preventive therapy. Development of a nucleic acid amplification test (NAAT) for LTBI could overcome these limitations by allowing targeting of preventive therapy at latently infected individuals with the highest risk of progression to active TB, with antimicrobial selection guided by genetic antimicrobial resistance profiling and capacity for test of cure on treatment completion.

TB patients (Group A): Inclusion Criteria: * Able and willing to give written informed consent to participate * Age ≥18 years * New diagnosis of smear-positive or Xpert-confirmed pulmonary TB * At least one asymptomatic adult household contact likely to fulfil TB contact eligibility criteria below Exclusion criteria: * More than 7 days of anti-TB treatment taken * Confirmed or suspected pregnancy (female participants) * Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study. Recent TB contacts (Group B): Inclusion Criteria: * Able and willing to give written informed consent to participate * Age ≥18 years * Household contact with an index case of smear-positive pulmonary TB in Group A above. Exclusion Criteria: * Clinical or radiological features of active TB * Current or previous anti-TB treatment * Confirmed or suspected pregnancy (female participants) * Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study. Historical TB contacts (Group C): Inclusion Criteria: * Able and willing to give written informed consent to participate * Age ≥18 years * Participant in previous TB household contact study Exclusion Criteria: * Clinical or radiological features of active TB * Current or previous anti-TB treatment * Confirmed or suspected pregnancy (female participants) * Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study.