Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Trial in Subjects Suspected to Have Tuberculosis, Comparing the Diagnostic Performance of C-Tb to QuantiFERON®-TB Gold In-Tube, in Combination With a Double Blind Randomized Split Body Safety Assessment of C-Tb Versus 2 T.U. Tuberculin PPD RT23 SSI (PPD)
Brief Summary: Tuberculosis (TB) continues to be one of the most serious bacterial infections worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB.

The new skin test is named C-Tb. Like the current tuberculin skin test, PPD, the C-Tb test is injected just under the skin and will, when positive, show redness and/or swelling at the injection site while a negative test will leave no reactions. The investigators hope that this new C-Tb skin test will be more precise (specific) than the PPD test, as the PPD test e.g. may show a reaction if the person tested is BCG vaccinated.

The aim of this trial is to test the C-Tb skin test in volunteers suspected of having TB disease.

With focus on age, HIV status and CD4 count the following analyses are done (in an overall perspective):

* To compare the C-Tb test to a blood test, the QuantiFERON test.
* To compare the C-Tb test to the PPD test that is currently being used.
* To assess the safety of the C-Tb test.


Options:
A: 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
B: Inclusion Criteria (HIV Negative patients):

* Has signed an informed consent
* Aged 18 to 65 years
* Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis
* Is HIV negative confirmed by 2 two rapid tests
* Is willing and likely to comply with the trial procedures
* Is prepared to grant authorized persons access to their medical record

Inclusion Criteria (HIV Positive patients):

* Has signed an informed consent
* Aged 18-65 years
* Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis
* Is HIV positive confirmed by:

  1. 2 positive rapid tests or
  2. 1 positive rapid tests and an additional confirmatory ELISA
* A CD4 count has been performed
* Is willing and likely to comply with the trial procedures
* Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

* Has been in treatment for TB for more than 2 weeks
* Has a known MDR/XDR-TB
* 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
* Has been tuberculin (TST) tested \< 12 months prior to the day of inclusion
* Is pregnant, breastfeeding or intending to get pregnant
* Is a female of child bearing potential not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures during the trial period
* Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
* Has a current skin condition which interferes with the reading of the skin tests e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
* Has a condition where blood drawings pose more than minimal risk for the patient, such as haemophilia, other coagulation disorders, or significantly impaired venous access
* 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
* Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
* Has a condition which in the opinion of the investigator is not suitable for participation in the study
C: 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.
D: 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

Answer: A