Table 2

Definitions of reference standards and diagnostic classifications

		Nicol et al	Nkereuwem et al	Barrio et al
Enrolment criteria	Inclusion criteria	Symptoms suggestive of TB (pulmonary)	Symptoms suggestive of TB (pulmonary)	Symptoms suggestive of TB (pulmonary and extrapulmonary) Controls: negative TST and QFT-GIT, and no signs or symptoms of TB
Enrolment criteria	Exclusion criteria	More than 72 hours of TB treatment or prophylaxis Not a resident in Cape Town	Not specified Presense of mediastinal lymphadenopathy alone	Anti-TB treatment for two or more weeks before enrolment HIV positivity or other known immunodeficiencies or immunosuppressive treatment
Symptoms of TB		Cough of any duration and at least one of the following: Household contact with an infectious tuberculosis source case within the preceding 3 months Loss of weight or failure to gain weight in the preceding 3 months Positive tuberculin skin test (TST) Suggestive CXR	Symptoms suggestive of pulmonary tuberculosis: Persistent or unremitting cough for more than 2 weeks And either weight loss, failure to thrive or persistent unexplained fever	Not specified
TB sampling and microbiological investigations		At least one induced sputum Xpert MTB/RIF or Xpert MTB/RIF Ultra and MGIT	At least one induced sputum Xpert MTB/Rif Ultra (all sites) and MGIT/LJ (not Nigerian site)	Three consecutive respiratory samples (induced or nasopharyngeal/nasogastric aspiration) Smear microscopy, Xpert MTB/RIF if positive smear microscopy OR abnormal X-ray
TB case classification	Confirmed TB	Any induced sputum culture or Xpert MTB/RIF positive for Mycobacterium tuberculosis	Bacteriological confirmation of M. tuberculosis (culture, Xpert MTB/RIF assay or both) from at least one respiratory specimen	Any sputum Xpert MTB/RIF positive for M. tuberculosis
	Unconfirmed TB	All children not defined as confirmed or unlikely TB	Bacteriological confirmation not obtained, and at least one (if TST/QFT-GIT pos) or two (if TST/QFT-GIT neg) of the following: Symptoms or signs suggestive of tuberculosis Chest radiograph consistent with tuberculosis Close tuberculosis exposure Positive response to tuberculosis treatment (requires documented positive clinical response to tuberculosis)	Bacteriological confirmation not obtained And positive TST/QFT-GIT and at least one of the following: X-rays consistent with TB Signs and symptoms of TB Close TB exposure, or Positive response to TB treatment OR if TST/QFT-GIT negative at least Two clinical criteria X-rays consistent with TB Signs and symptoms of TB Close TB exposure, or Positive response to TB treatment
	Unlikely TB	All of the following: TB culture negative No tuberculosis treatment given Documented improvement of symptoms and signs at follow-up visit	Bacteriological confirmation not obtained and criteria for unconfirmed tuberculosis not met	Only evidence of M. tuberculosis infection or presented only one clinical criterion compatible with TB Controls: negative TST and QFT-GIT, and no signs or symptoms of TB
Definition of reference standards	Microbiological reference standard (MRS)	Positive=confirmed TB Negative=unconfirmed and unlikely TB	Positive=confirmed TB Negative=unconfirmed and unlikely TB	Positive=confirmed TB Negative=unconfirmed and unlikely TB+controls
Definition of reference standards	Composite reference standard (CRS)	Positive=confirmed and unconfirmed TB Negative=unlikely TB	Positive=confirmed and unconfirmed TB Negative=unlikely TB	Positive=confirmed and unconfirmed TB Negative=unlikely TB+controls

FN, false negative; FP, false positives; QFT-GIT, QuantiFERON-TB Gold In-Tube; TB, tuberculosis; TN, true negatives; TP, true positives.