Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa
Brief Summary: The purpose of this study is to compare three strategies for finding TB cases in a rural Sub-Saharan African setting: 1) Screening all attendees of primary care clinics for TB; 2) Conducting household contact investigations of newly diagnosed TB cases; 3) Providing incentives to newly diagnosed TB cases and their contacts to promote contact screening for TB. For each intervention, investigators will measure comparative effectiveness in terms of cases identified as well as the cost-effectiveness and feasibility of implementation.


Options:
A: Inclusion Criteria:

Facility-based screening arm

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Attending any of the study 28 study clinics in the facility-based screening arm

Contact tracing arm- Index Case

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Newly diagnosed (last 2 months) with TB at any of the 28 study clinics in the contact tracing arm

Contact tracing arm- Household Contact

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Living in the same household as an enrolled Index case (see above)

Contact tracing arm- Non-household Close Contact

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Referred to the study as a close contact of an enrolled Index case (see above)

Exclusion Criteria (all arms):

* Unable to provide informed consent.
B: Inclusion Criteria:

HIV NEGATIVE PARTICIPANTS:

1. Participants between 5 and 65 years attending the TB clinic due to suspicion of TB disease
2. Infants, toddlers and children between 28 days and 4 years must either have symptoms or signs of TB or be in close contact to a smear positive pulmonary TB case (more than 6 hours/day for at least five days)
3. Is between 28 days and 65 years of age
4. Participant, parent or legal guardian has signed the informed consent
5. Is HIV negative confirmed by two rapid tests. However, children between 28 days and 4 years may have an unknown HIV status and may receive antiretroviral therapy (ART) or have breastfeeding mothers on ART
6. Is willing and likely to comply with the trial procedures
7. Is prepared to grant authorized persons access to their medical record

HIV POSITIVE PARTICIPANTS:

1. Participants between 5 and 65 years attending the TB clinic due to suspicion of TB disease
2. Infants, toddlers and children between 28 days and 4 years must either have symptoms\* or signs\*\* of TB or be in close contact to a smear positive pulmonary TB case (more than 6 hours/day for at least five days)
3. Is between 28 days and 65 years of age
4. Participant, parent or legal guardian has signed the informed consent
5. Is HIV positive confirmed by:

   1. two positive rapid tests or
   2. 1 positive rapid test and an additional confirmatory ELISA test
6. A CD4 count has been done
7. Is willing and likely to comply with the trial procedures
8. Is prepared to grant authorized persons access to their medical record

HIV NEGATIVE CONTROL GROUP:

1. Participant with no known contact to people infected with MTb and no signs or symptoms of TB.
2. Is between 5 and 11 years of age
3. Participant, parent or legal guardian has signed the informed consent
4. Is HIV negative confirmed by two rapid tests
5. Is willing and likely to comply with the trial procedures
6. Is prepared to grant authorized persons access to their medical record

Exclusion Criteria:

HIV NEGATIVE PARTICIPANTS:

1. Has a confirmed diagnosis of tuberculosis at Screening Visit
2. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines) except BCG vaccine
3. Has been tuberculin (TST) tested less than 12 months prior to the day of inclusion
4. Is pregnant, breastfeeding or intending to get pregnant during the trial period
5. Is a female of child bearing potential (12 years of age or older) not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures during the trial period
6. Has an active disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
7. Has a current skin condition which interferes with the reading of the C-Tb and PPD e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
8. Has a condition where blood drawings pose more than minimal risk for the participant, such as haemophilia, other coagulation disorders or significantly impaired venous access
9. Currently participating in another clinical trial with an investigational or non-investigational drug or device or has participated in another clinical trial within the 3 months prior to dosing
10. Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
11. Has a condition which in the opinion of the investigator is not suitable for participation in the trial

HIV POSITIVE PARTICIPANTS:

1. Has a confirmed diagnosis of tuberculosis at Screening Visit
2. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)
3. Has been tuberculin (TST) tested less than 12 months prior to the day of inclusion
4. Is pregnant, breastfeeding or intending to get pregnant during the trial period
5. Is a female of child bearing potential (12 years of age or older) not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures during the trial period
6. Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
7. Has a known diagnosis of AIDS or is receiving antiviral therapy at the time of Screening Visit
8. Has a current skin condition which interferes with the reading of the C-Tb and PPD e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
9. Has a condition where blood drawings pose more than minimal risk for the participant, such as haemophilia, other coagulation disorders or significantly impaired venous access
10. Currently participating in another clinical trial with an investigational or non-investigational drug or device or has participated in another clinical trial within the 3 months prior to dosing
11. Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
12. Has a condition which in the opinion of the investigator is not suitable for participation in the trial

HIV NEGATIVE CONTROL GROUP:

1. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines) except BCG vaccine
2. Has been tuberculin (TST) tested less than 12 months prior to the day of inclusion
3. Has an active disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
4. Has a current skin condition which interferes with the reading of the C-Tb and PPD e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
5. Has a condition where blood drawings pose more than minimal risk for the participant, such as haemophilia, other coagulation disorders, or significantly impaired venous access
6. Currently participating in another clinical trial with an investigational or non-investigational drug or device, or has participated in another clinical trial within the 3 months prior to dosing
7. Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
8. Has a condition which in the opinion of the investigator is not suitable for participation in the trial
C: Inclusion Criteria:

* children aged from 0 to 13 years
* confirmed HIV infection
* suspicion of tuberculosis
* informed consent signed by at least one parent or guardian
* on ARVs or not

Exclusion Criteria:

* history of anti TB treatment started in the past 2 years
* on going tuberculosis treatment
* Suspicion of exclusive extra-thoracic tuberculosis
D: Inclusion Criteria:

1. Can comply with one of the following groups:

   1. Negative control group: Must have no history of exposure to a TB index case, and have no signs or symptoms of TB
   2. Positive control group: Confirmed TB disease within the last 3 years by sputum smear microscopy and/or Culture, Gene Xpert or PCR
   3. Close contact group: Must be in close contact with a pulmonary smear positive TB index case for more than 6 hours/day for at least five days
   4. Occasional contact group: Must be in contact with a pulmonary sputum smear positive TB index case between 6 hours/week and 6 hours/day
2. Is between 6 weeks - 65 years of age
3. Participant, parent or legal guardian has provided signed informed consent
4. Is willing and likely to comply with the trial procedures
5. Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

1. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. Mumps Measles Rubella (MMR), yellow fever, oral typhoid vaccines)
2. Has been tuberculin tested less than 12 months prior to the day of inclusion
3. Is pregnant, breastfeeding or intending to get pregnant within the trial period
4. Is a female of child bearing potential (12 years of age or older having had their first menstruation) not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures within the trial period
5. Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
6. Has a current skin condition which interferes with the reading of the C-Tb and Tuberculin PPD RT23 SSI e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
7. Has a condition where blood drawings pose more than minimal risk for the participant, such as haemophilia, other coagulation disorders, or significantly impaired venous access
8. Current participation in another clinical trial with an investigational or non investigational drug or device, which in the opinion of investigator may interfere with this trial drug
9. Has participated in previous clinical trials investigating injections with ESAT-6 and/or CFP-10 antigens
10. Has a condition which in the opinion of the investigator is not suitable for participation in the trial

Answer: A