Please select the eligibility criteria that correspond to the clinical trial below.
Title: Tuberculosis Research of INA-RESPOND On Drug Resistance
Brief Summary: This study is a prospective observational cohort study of TB patients who are treated or evaluated at 10 study sites. Patients presenting with cough for 2 weeks or longer with at least one additional TB symptom and a chest X-ray suggestive of TB, will be invited to be enrolled in the study. The signed informed consent will designate their willingness to participate on this study.


Options:
A: Inclusion Criteria:

Case Detection Group:

* Age 18 years or above
* Clinical suspicion of pulmonary TB (including cough ≥2 week and at least 1 other symptom typical of TB);
* Willingness to provide 3-4 sputum specimens at enrolment;
* Willingness to have a trial follow-up visit approximately 2 months after enrolment;
* Provision of informed consent.

Drug Resistant TB Group:

In addition to the criteria of the Case Detection Group, participants should also meet the following conditions:

* Non-converting pulmonary TB cases (category I and category II failures)

Exclusion Criteria:

Case Detection Group:

* Receipt of any dose of TB treatment within 60 days prior to enrolment (even if within last two days only).

Drug Resistant TB Group:

* Receipt of any dose of MDR-TB treatment within 60 days prior to enrolment (even if within last two days only).
B: Key Inclusion Criteria

1. Provide written, informed consent prior to all trial-related procedures (if under 18, include consent of legal guardian).
2. Body weight of ≥35 kg (in light clothing and no shoes).
3. Male or female, aged 14 years or above.
4. Subjects with one of the following pulmonary TB conditions (WHO definitions prior to 2021):

   a. Extensively Drug Resistant Tuberculosis (XDR-TB) with

   i. documented culture positive (for M.tb.) results within 3 months prior to screening or M.tb. confirmed in sputum based on molecular test within 3 months prior to or at screening;

   ii. documented resistance to isoniazid, rifamycins, a fluoroquinolone and an injectable historically at any time or at screening;

   b. Multi-Drug Resistant Tuberculosis (MDR-TB) documented by culture positive results (for M.tb.) within 3 months prior to or at screening with documented non-response to treatment with the best available regimen for 6 months or more prior to enrolment who in the opinion of the Investigator have been adherent to treatment and will be adherent to study regimen;

   c. MDR-TB documented by culture positive (for M.tb.) results within 3 months prior to or at screening who are unable to continue second line drug regimen due to a documented intolerance to:

   i. PAS, ethionamide, aminoglycosides or fluoroquinolones;

   ii. Current treatment not listed above that renders subject eligible for the study in the Investigator's opinion.

6. Chest X-Ray picture (taken within a year prior to screening) consistent with pulmonary TB in the opinion of the Investigator.

Key Exclusion Criteria

1. Karnofsky score \< 50 within 30 days prior to entry.
2. Body Mass index (BMI) \< 17 kg/m²
3. History of allergy or known hypersensitivity to any of the trial Investigational Medicinal Products or related substances.
4. HIV infected Subjects having a CD4+ count ≤ 50 cells/μL
5. Having participated in other clinical studies with dosing of investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational study that includes treatment with medicinal agents. Subjects who are participating in observational studies or who are in a follow up period of a trial that included drug therapy may be considered for inclusion.
6. Significant cardiac arrhythmia requiring medication.
7. Subjects with the following at Screening:

   1. QTcF interval on ECG \>500 msec.
   2. History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
   3. Clinically significant ventricular arrhythmias;
   4. Subjects with other cardiac abnormalities that may place them at risk of arrhythmias must be discussed with the sponsor medical monitor before enrolment. Such abnormalities include: Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome); Electrocardiographic evidence of complete or clinically significant incomplete left bundle branch block or right bundle branch block; Evidence of second or third degree heart block; Intraventricular conduction delay with QRS duration more than 120 msec.
8. Females who have a positive pregnancy test at Screening or already known to be pregnant, breastfeeding, or planning to conceive a child during the study or within 6 months of cessation of treatment. Males planning to conceive a child during the study or within 6 months of cessation of treatment.
9. A peripheral neuropathy of Grade 3 or 4, according to DMID (Appendix 2). Or, subjects with a Grade 1 or 2 neuropathy which is likely to progress/worsen over the course of the study, in the opinion of the Investigator.
10. Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) or prior use within 2 weeks of treatment assignment.
11. Subjects with the following toxicities at Screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007):

    a. serum potassium less than the lower limit of normal for the laboratory; b. Hemoglobin level grade 2 or greater (\< 8.0 g/dL); c. Platelets grade 2 or greater(\<75,000/mm3); d. Absolute neutrophil count (ANC) \< 1000/ mm3; e. Aspartate aminotransferase (AST) \> 3 x ULN g. Total bilirubin \> or = to 2xULN h. Direct bilirubin \> ULN i. Serum creatinine level greater than 2 times upper limit of normal j. Albumin \<32 g/L
C: Inclusion Criteria:

* Patients suspected of having pulmonary TB
* Cough ≥ 2 weeks
* At least one other TB clinical symptom

  * Fever
  * Unexplained weight loss
  * Loss of appetite
  * Hemoptysis
  * Shortness of breath
  * Chest pain
  * Night sweats
  * Fatigue
* Suggestive TB on chest x-ray based on pulmonologist or internist consultant of pulmonology opinion
* Age ≥ 18 years' old
* Willing to be treated or evaluated at study site
* Willing to have specimens stored for use in future studies
* Patient denies having TB treatment for more than 7 days in the last 1 month (30 days).

Exclusion Criteria:

Pregnancy or any serious condition includes, but not limited to, liver disease, chronic kidney disease, and psychiatric illness that might interfere with study compliance (based on the clinician judgment).
D: Inclusion Criteria:

* The patient is willing to provide specimens (urine, blood, stool, respiratory tract specimens and swabs)
* The patient is clinically suspected of having TB (Two WHO TB symptoms for HIV negative patients and one WHO TB symptom if HIV positive)

Exclusion Criteria:

* The patient is under the age of 18 years old
* The patient declines consent
* The patient has too few clinical symptoms for TB

Answer: C