Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II/III Trial Investigating if Concomitant Injections of the Diagnostic Agents C-Tb and 2 T.U Tuberculin PPD RT 23 SSI Affect the Induration Responses in Combination With a Safety Assessment of C-Tb
Brief Summary: A new, more specific skin test to detect tuberculosis has been developed by Statens Serum Institut in Denmark. The new skin test is named C-Tb and like the current Tuberculin a positive test result will show as redness and/or induration at the injection site, while a negative test will leave no reactions.

The aim of this study is to address if the size of induration and the sensitivity of C-Tb is influenced by concomitant injections of C-Tb and Tuberculin. Furthermore, the intention is to evaluate the safety of C-Tb when injected alone or concomitantly with Tuberculin.


Options:
A: Inclusion criteria:

1. Children aged 2 to 59 months
2. Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with:

   1. Peripheral oxygen saturation \< 90% or central cyanosis, or
   2. Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or
   3. Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea) and/or chest indrawing, with any of the following danger signs:

      * Inability to breastfeed or drink,
      * Persistent vomiting
      * Lethargy or reduced level of consciousness
      * Convulsions,
      * Stridor in calm child
      * Severe malnutrition
3. Informed consent signed by parent/guardian

Exclusion criteria:

- Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months
B: 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.
C: 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
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: C