Evaluation of Centralised TB Assay Solutions
Evaluation of Centralised TB Assay Solutions
Tuberculosis (TB) remains a life-threatening disease partly due to increasing incidence of
 multidrug and extensively drug-resistant TB. Diagnostic based on culture and conventional
 drug susceptibility testing using media take several weeks leading to prolonged periods of
 ineffective therapy and ongoing transmission. Development of rapid molecular diagnostic tests
 for the identification of Mycobacterium tuberculosis (MTB) and drug resistance has become a
 high priority.

 The Xpert® MTB/RIF Assay does not provide information on INH-resistance and the LPA is only
 recommended for use in smear-positive samples, complex to perform and requires manual
 interpretation. Several novel assays have been recently developed/CE-marked offering high
 sample throughput and higher sensitivity for detection of MTB, RIF- and INH-resistance in
 centralized laboratories. However, published data on their performance and operational
 characteristics is extremely limited.

 This is a prospective, multicentre, diagnostic accuracy trial in which the performance of
 centralised TB assay solutions will be assessed at the intended setting of use with culture,
 phenotypic DST and sequencing as reference standard.

 Potential trial participants will be identified at participating TB clinics or hospitals
 (enrolment sites). Sputum samples will be collected and transported to the associated TB
 reference laboratories (testing sites).

 In order for the results of this trial to be generalizable, adults with symptoms compatible
 with pulmonary TB undergoing evaluation will be screened for inclusion at geographically
 diverse participating centres in high burden TB countries. Additionally, to supplement the
 drug-resistant cases to timely achieve accurate performance estimates, well-characterized
 frozen sputum samples from the FIND specimen bank will be used.
Inclusion Criteria:

 Patients are eligible to be included as trial participants only if all of the following
 inclusion criteria apply:

 -  Aged ≥18 years

 -  Clinical suspicion of pulmonary TB including cough ≥2 weeks (or any duration if HIV
 positive ) and ≥1 other symptom typical of pulmonary TB listed below:

 -  Fever

 -  Malaise

 -  Recent weight loss

 -  Night sweats

 -  Contact with active case

 -  Haemoptysis

 -  Chest pain

 -  Loss of appetite

 Exclusion Criteria:

 Participants are excluded from the trial if any of the following exclusion criteria apply:

 -  Unwilling or unable to provide informed consent

 -  Unwilling to provide four sputum specimens at enrolment i.e. 2x sputa on day 1 and 2x
 sputa on day 2 (up to 1 week from enrolment)

 -  Patients with only extra-pulmonary TB signs & symptoms

 -  Receipt of any dose of TB treatment within 6 months prior to enrolment