Table 2.

NIH and P1041 TB classification definitions and correlation as listed

NIH definitions and classification of TB endpoints	P1041 protocol-defined classification of TB endpoints
Confirmed TB cases will be children with at least 1 sign or symptom* suggestive of TB and microbiologically confirmed TB, defined as at least 1 positive culture with M. tb speciation from a specimen representative of intrathoracic disease.	Definite Pulmonary TB cases must have M. tb isolated on gastric washing and/or induced sputum.
Probable TB cases will include children with at least 1 sign or symptom suggestive of TB and a chest radiograph (CXR) consistent with intrathoracic TB and at least 1 of the following: (1) positive clinical response to anti-TB therapy, (2) documented exposure to a household or close contact with a TB case, or (3) immunologic evidence of infection with M. tb infection by a positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA).	Probable Pulmonary TB cases must have positive AFB (auramine fluorochrome, most commonly used in South Africa, or Ziehl Neelson (ZN)) stain on a specimen obtained by gastric washings or induced sputum in a child who fulfills at least one of the following: Presence of at least 2 clinical criteria: Cough > 2 weeks duration Family history of PTB in the prior 24 weeks Reactive TST (>5 mm in an HIV +, >10 mm in HIV−) Weight <3rd percentile for age or a decrease in weight that has crossed 2 major growth percentiles since the last documented weight Fever of unknown origin >2 weeks duration OR Abnormal chest x-ray with at least one of the following: Hilar lymphadenopathy Paratracheal lymphadenopathy Alveolar consolidation Miliary pattern Lung parenchymal breakdown/cavitation Ghon focus
Possible TB cases will include children with at least 1 sign or symptom suggestive of TB and who have either: (1) a CXR that is consistent with intrathoracic TB or (2) at least 1 of the following: (a) positive clinical response to anti-TB therapy, (b) documented exposure to a household or close contact with a TB case, or (c) immunologic evidence of infection with M. tb (TST or IGRA positivity).	Possible TB cases will have both: Abnormal chest x-ray (see criteria above) One of the following: Positive TST (≥5mm in HIV-infected and ≥10 mm in HIV-uninfected),OR Scores ≥ 6 on the algorithm to diagnose clinical TB (see Table 1)
Tuberculosis unlikely cases are symptomatic but not fitting the above definitions and no alternative diagnosis established.	See footnote** Not protocol defined TB or clinical TB
Not tuberculosis cases fit the diagnosis for tuberculosis unlikely but with an established alternative diagnosis.	Not TB are those cases evaluated for TB but with an established alternative diagnosis. Latent TB infection are those cases have positive TST (as defined above) but do not meet any of the above definitions.***

^*

NIH: Clinical signs/symptoms suggestive of TB (i.e. entry points/criteria):

1. Persistent (>2 weeks), nonremitting cough.
2. Weight loss/failure to thrive: unexplained weight loss: >5% reduction in weight compared with the highest weight recorded in last 3 months, or failure to thrive: Clear deviation from a previous growth trajectory and/or documented crossing of 1 or more major percentile lines in the preceding 3 months and/or weight-for-age z score of ≤−2 in the absence of information on previous/recent growth trajectory and/or weight-for-height z score of ≤−2 in the absence of information on previous/recent growth trajectory and not responding to nutritional rehabilitation (or antiretroviral therapy if HIV-infected).
3. Persistent (>1 week), unexplained fever (>38°C) reported by a guardian or objectively recorded at least once.
4. Persistent, unexplained lethargy or reduced playfulness reported by the parent/caregiver.

^**Not protocol defined TB cases are those cases that were evaluated by the P1041 ERG but did not meet protocol defined definitions of TB. These cases were prescribed anti-TB therapy by an attending physician who was not a member of the study team.

^***Note, we will not evaluate LTBI cases that were determined at week 96 or beyond, because these were not TB suspects. They have a diagnosis based on TST done per protocol schedule of evaluations rather than due to clinical suspicion of TB disease.