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Understanding NIH clinical case definitions for pediatric intrathoracic TB by applying them to a clinical trial
C A Beneri1, L Aaron2, S Kim3
1Department of Pediatrics, Stony Brook School of Medicine, Stony Brook, New York, New York, USA.
Insights
Standardized pediatric tuberculosis (TB) classification guidelines showed poor agreement when applied to infants in a clinical trial. This highlights the need to adapt definitions for active surveillance cases in pediatric TB diagnosis.
Area of Science:
- Pediatric infectious diseases
- Clinical trial methodology
- Public health surveillance
Background:
- Standardized clinical case definitions are crucial for accurate pediatric tuberculosis (TB) diagnosis and classification.
- Published guidelines for intrathoracic TB classification are primarily designed for passive case finding.
Purpose of the Study:
- To evaluate the application of existing intrathoracic TB classification guidelines in a pediatric trial (P1041) using active surveillance.
- To assess the agreement between protocol-defined and National Institutes of Health (NIH) classifications for presumed TB patients.
Main Methods:
- Retrospective cross-classification of presumed TB patients from the P1041 trial using protocol-defined and NIH criteria.
- Assessment of agreement between the two classification systems.
Main Results:
- Of 219 TB suspects, 158 were classified as TB (21 confirmed, 92 probable, 45 possible), with weight loss and failure to thrive being common signs.
- Agreement between classification definitions was poor among patients with signs/symptoms.
- A significant number of presumed TB cases (53) lacked signs/symptoms, including 33 classified as TB by the P1041 protocol.
Conclusions:
- The poor agreement between P1041 and NIH classifications is attributed to differences between active surveillance (P1041) and passive case finding (intended NIH use).
- Standardized definitions need adaptation for presumed TB patients identified through active surveillance.
- Future efforts should expand TB disease classification to encompass active surveillance findings.
Setting:
Standardized clinical case definitions represent the best option for pediatric tuberculosis (TB) disease diagnosis and classification.
Objective:
To apply published guidelines for intrathoracic TB classification for use in reporting diagnostic studies with passive case finding to presumed TB patients from International Maternal Pediatric Adolescent AIDS Clinical Trials P1041, a trial of isoniazid prophylaxis in healthy human immunodeficiency virus exposed, bacille Calmette-Guérin vaccinated infants which employed active surveillance to assess a novel application of these guidelines in this setting.
Methods:
P1041 presumed TB patients were retrospectively cross-classified by protocol-defined and National Institutes of Health (NIH) classifications, and agreement was assessed.
Results:
Of 219 TB suspects, 166 had signs/symptoms, with 158 considered TB (21 confirmed, 92 probable, 45 possible) and 8 not TB (6 TB unlikely, 2 alternative diagnoses). Weight loss and failure to thrive represented the majority of the observed signs/symptoms. Among those with signs/symptoms, agreement between definitions was poor. Furthermore, 53 TB presumptives were without signs/symptoms, including 33 classified by the P1041 protocol as TB.
Conclusion:
Poor agreement between P1041 and NIH classifications reflects cases identified through active vs. passive surveillance, the latter reflecting the intended use of NIH definitions. Given the interest in standardized definitions for broader application, future efforts could focus on expanding TB disease classification to presumed TB patients identified through active surveillance.
