Table 3.

Diagnostic components included in NIH definition and corresponding criteria applied to the P1041 data base

Diagnostic components	Summary of NIH definitions	Criteria applied to P1041 data base
Microbiologic confirmation	At least one positive culture (with confirmed M. tb speciation) from sputum	At least one positive culture, defined as M. tb isolated on gastric washing and/or induced sputum
Clinical signs and symptoms suggestive of tuberculosis1	Persistent cough (>2 weeks, unremitting)	Any cough (>2 weeks) present at TB diagnosis
	Persistent unexplained fever (>1 week, >38°C)	Any fever (>1 week) present at TB diagnosis
	Persistent, unexplained lethargy or reduced playfulness	Any lethargy present at TB diagnosis
	Unexplained weight loss >5% reduction in weight compared to the highest weight recorded in the last 3 months	Any weight loss >5% reduction in weight compared to the highest weight recorded in the last 3 months, assessed at TB diagnosis or closest prior visit within 3 months.1
	One of following indicators of FTT: (1) clear deviation from a growth trajectory, (2) documented crossing of percentile lines in preceding 3 months, (3) weight-for-age z-score ≤−2 in the absence of previous/recent growth trajectory or weight-for-height z-score ≤−2 in the absence of previous/recent growth trajectory. In addition, not responding to nutritional rehabilitation (or ARV if HIV infected).	One of the following: (1) documented diagnosis of FTT present at TB diagnosis, (2) weight-for-age or weight-for-height that crossed one major percentile line (3, 10, 25, 50, 75, 90, 97) within a 3-month period, recorded in the preceding 3 months1, (3) weight-for-age z-score or weight-for-height z-score ≤−2 in the preceding 3 months.1 Data on response to nutritional rehabilitation was not available.
	Additional signs and symptoms suggestive of TB for infants 0–60 days include (a) neonatal pneumonia, (b) unexplained hepatosplenomegaly, or (c) sepsis-like illness	Data not available. All infants in P1041 were at least 91 days of age at enrollment.
Interpretation of CXR	CXR reading and reporting procedure: minimum of 2 independent and blinded readers, a third expert reader in case of discordant reading, overall quality of CXR indicated, and standardized forms. CXR is classified as “consistent with tuberculosis” if there is a positive response for any 1 of the following radiographic features at the same location, by at least 2 expert reviewers: airway compression and/or tracheal displacement, soft tissue density suggestive of lymphadenopathy, air space opacification, widespread bilateral nodular picture, either miliary or larger lesions, pleural effusion, cavities, ghon focus, or vertebral spondylitis.	CXRs not required to be read by more than one reader. Acceptable quality of CXR indicated. Positive response for any 1 of the following radiographic features: airway compression and/or tracheal displacement, soft tissue density suggestive of lymphadenopathy, air space opacification, widespread bilateral nodular picture, either miliary or larger lesions, pleural effusion, cavities, or ghon focus, within 3 months of TB diagnosis.
Tuberculosis exposure	History of exposure to M. tb was defined as reported exposure to a case of TB (household/close contact with documented or verbal report of smear positive and/or culture positive TB or TB treatment), within preceding 24 months	Reported exposure to a case of TB (household or non-household contact with a positive TB result or receipt of TB treatment), within preceding 24 months.
	Immunologic evidence of M. tb infection was defined as either (1) a positive tuberculin skin test (using 5TU PPD or 2TU RT23) defined as ≥10 mm if HIV uninfected or ≥ 5 mm if HIV-infected or severely malnourished or (2) a positive IGRA test	TST of ≥10 mm for HIV-uninfected or ≥ 5 mm for HIV-infected or severely malnourished patient, within 3 months1 of TB diagnosis. IGRA testing was not conducted as part of the diagnostic work up for TB in P1041.
Response to anti-tuberculosis treatment	Appropriate anti-TB treatment should meet the following criteria: treatment with standard regimens in accordance with local or international treatment guidelines and satisfactory adherence proposed as 80% adherence by pill count or self-reported. Response to anti-TB treatment should be evaluated at 2 months after anti-TB treatment has commenced using standardized forms with tick-box options for recording. Response to anti-TB therapy was defined as clinical features suggestive of TB disease that were present at baseline have improved, and there is no new clinical feature suggestive of TB.	TB patients in P1041 were not evaluated specifically for response to anti-TB treatment, as described in the NIH consensus guidelines. Response to treatment was based on resolution of sign/symptoms, diagnoses and changes in anthropometric measurements. A positive response to anti-tuberculosis treatment was defined as 1) resolution or improvement in all clinical signs/symptoms (as defined above) that contributed to the TB diagnosis or documentation that TB diagnosis resolved within 3 months1 after treatment initiation, and 2) no new clinical signs/symptoms within 3 months1 after treatment initiation. Data on adherence to anti-TB treatment was not available.

¹A 4-week allowance was added to the 3 month windows during which S/S and response to anti-TB treatment were evaluated for consistency with the P1041 study visit schedule and to allow for late visits.