The ERASE - TB study will be conducted in order to fill a critical unmet need for tuberculosis control. Persons who are in contact with an infectious TB case may become infected themselves. Among those who are infected, most will stay healthy but some will develop TB themselves.

These people would benefit from preventive treatment, which would also stop TB from being spread to other persons.

The problem currently is that it is impossible to determine with certainty who would require preventive treatment, and who will remain healthy. Out of 100 persons exposed to an infectious TB patient, only 2 will go on to have TB according to a study in Vietnam, but there are no good tests available to identify those with a risk for TB disease. Treating 100 persons to prevent 2 cases of TB is not effective, so preventive treatment is not used in adults and adolescents in Tanzania, Mozambique and Zimbabwe, where this study will be conducted, but also in many other settings.

The ERASE - TB project will evaluate a number of newly developed diagnostic tests, to see which of those will be able to predict TB in persons at risk, and therefore steer preventive treatment well.

For this, the investigators will invite 2,100 household contacts (HHC) of infectious TB patients, who are at least 10 years old, into the study. Everyone will be examined initially, and again in regular intervals, for 1.5 to 2 years; and whenever the participants will present with symptoms that could indicate that they develop TB.

At every visit, the investigators will perform an X-ray and take some blood and urine samples to perform new candidate tests. At the first/baseline visit, all household contacts without TB will undergo a spirometry to evaluate their pulmonary function.

If someone is unwell, the investigators will also examine sputum for the presence of TB bacilli. In the end, the investigators will then be able to say who of the persons in the study developed TB, and who remained healthy. From all samples taken at different timepoints, the investigators will then determine which test found TB early, and clearly distinguished between persons developing TB, and persons who would remain healthy .

Inclusion Criteria:

TB index case:

• Aged at least 18 years
• Having at least one other person living in the household aged ≥10 years
• Written informed consent to conduct socio-economic and clinical questionnaire, to provide a sputum sample for culture and sequencing, and to approach the household members.
• Recently diagnosed with active pulmonary TB within the last 4 weeks
• Has taken less than 7 daily doses of anti-TB treatment since diagnosis; ensuring a positive culture can still be obtained
• Able to spontaneously produce sputum
• Sputum microscopy positive in Ziehl-Neelsen or Auramine-O staining of ideally 2+ or higher, but at least 1+ on the IUATLD/WHO scale, OR (in case no sputum microscopy done) GeneXpert positive, at least TB "medium"
• A firm home address, maintained unchanged for the last 6 months, that is accessible to visiting

Household Contact:

• Aged at least 10 years
• Written informed consent for study participation, including HIV testing, and home visits by the study team for follow-up (for minors <18 yr.: consent of the parent/guardian, assent of the participant)
• Recent (in the last 4 weeks), substantial exposure to an infectious TB case in the household, defined as sleeping at least 3/7 nights in the same household
• If HIV negative: not on preventive therapy (preventive therapy is not an exclusion criterion for HIV positive persons)

Exclusion Criteria:

Household Contact

• Circumstances that raise doubt on free, uncoerced informed consent (e.g. in a mentally handicapped person)
• Prisoners
• Recent treatment for active TB, completed within the last 30 days OR on current TB treatment for active TB.

TB index cases will be recruited at the primary health care clinics where the patient is receiving TB treatment. Household contacts have substantial recent exposure to the TB index case in the household (defined as sleeping at least 3/7 nights in the same household in the last 4 weeks).

Accordance with EU General Data Protection Regulation and local data protection law needs to be worked out.