Please select the eligibility criteria that correspond to the clinical trial below.
Title: Feasibility, Accuracy, and Effect of Point-of-care Xpert MTB/RIF Ultra and Xpert MTB/RIF Ultra Testing in Patients Suspected of Having TB: a Randomised Controlled Trial
Brief Summary: TB is a global health problem and in South Africa rates as the second most important problem in terms of Burden of Disease. There are many reasons for this, among which are diagnostic difficulties, extended treatments, drug resistance and health care provision. This application is concerned with all these drivers and will focus activities on a clinic which provides basic care in a very deprived socio-economic area of greater Cape Town, South Africa.

Patients studied in routine, but demanding environments are our focus as these clinics are representative of many areas where TB (and HIV) are found at high prevalence. If the constraints of working in such areas can be understood and appropriate changes that work made, the investigators believe the outputs and policy changes generated in this study will contribute to future success in other settings.

The investigators wish to study the implementation of the Xpert®MTB/RIF (Xpert) and Xpert Ultra (Ultra) systems in situ using a randomised controlled trial design, as opposed to a remote site (central laboratory), to assess whether time to diagnosis can be improved using point of care (POC). The investigators wish to maximise this opportunity by collecting biological samples from a patient population experiencing a TB epidemic for the evaluation of future TB diagnostics.

Using human DNA, the investigators will attempt to determine reasons for poor or no treatment response. Two possibilities exist for this: a) the M. tuberculosis strain is resistant to the drug in question or b) the patient is highly susceptible to the bacterium. The investigators will determine the exome sequences of study participants with susceptible M. tuberculosis strains who show poor or no response, and compare this with rapid responders. Using 16S rRNA sequencing, the investigators will also observe how the microbiome of TB patients is altered during TB treatment and how this is associated with treatment outcome, as well as after TB treatment.

This project will set the foundation for the implementation of new POC TB diagnostic technologies in clinics in South Africa. The biobanked specimens collected can be rapidly utilised for nascent technologies. Studying the patient microbiome will provide insights into what makes some patients more susceptible to TB and what microbiological changes occur during the course of anti-TB treatment.


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: Inclusion Criteria:

* HIV-positive
* 18 years and above
* Able to give informed consent
* Admitted at the wards attached to the research site ART/HIV-clinic
* Eligible for LF-LAM testing (defined by WHO in the LF-LAM policy update 2019): CD4-cell-count ≤200 cells/μL (the last measured CD4-cell-count); or a WHO clinical stage 3 or 4 event at presentation for care; or seriously ill defined by WHO (respiratory rate \> 30/min, temperature \> 39°C, heart rate \> 120/min or unable to walk unaided); or a positive WHO TB symptom screening including one of the following symptoms: current cough, fever, weight loss, or night sweats

Exclusion Criteria:

* Anti-tuberculous treatment including preventive treatment with Isoniazide within the last 60 days
* Earlier participation in the same study
C: 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
D: Inclusion Criteria:

* Suspected pulmonary TB.
* Ability and willingness of candidate or legal guardian/representative to provide informed consent.
* Men and women age equal to or greater than 18 years.

Exclusion Criteria:

* Either receipt of ≥48 cumulative hours OR three or more doses of anti-TB treatment within 180 days prior to completion of second sputum collection for Xpert testing

Answer: C