Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

BACKGROUND: International (National Institutes of Health [NIH]) case definitions have been proposed for paediatric tuberculosis (TB) diagnostic studies. The relevance of these definitions for contact tracing studies is unknown.

METHODS: We developed case definitions for a community-based contact tracing diagnostic study. We compare disease certainty using protocol-defined and NIH case definitions and describe TB disease spectrum and severity.

RESULTS: There were 111 potential disease episodes in 109 (21% human immunodeficiency virus [HIV] infected) of 1093 children enrolled. Based on NIH definitions, there were 8 confirmed, 12 probable, 17 possible and 3 unlikely TB and 2 non-TB episodes. Using protocol case definitions, there were 23 episodes of confirmed, 36 probable, 27 possible and 0 unlikely TB and 21 non-TB. Of 111 potential episodes, 69 were unclassifiable using the NIH definition, while 4 were unclassifiable using the protocol definition. Agreement between definitions was 0.30 (95%CI 0.23–0.38). There were 62 episodes (72%) of non-severe and 24 (28%) of severe TB.

CONCLUSIONS: The NIH definition had limited applicability to household contact studies, despite the wide spectrum of disease observed. Further research is needed to develop case definitions relevant to different research settings, including contact investigation to capture the wide spectrum of paediatric TB in clinical research.