Research article |

Evaluation of Tuberculosis Diagnostics in Children

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

Authors: Stephen M. Graham, Tahmeed Ahmed, Farhana Amanullah, Renee Browning, Vicky Cardenas, Martina Casenghi, Luis E. Cuevas, Marianne Gale, Robert P. Gie, Malgosia Grzemska, Ed Handelsman, Mark Hatherill, Anneke C. Hesseling, Patrick Jean-Philippe, Beate Kampmann, Sushil Kumar Kabra, Christian Lienhardt, Jennifer Lighter-Fisher, Shabir Madhi, Mamodikoe Makhene, Ben J. Marais, David F. McNeeley, Heather Menzies, Charles Mitchell, Surbhi Modi, Lynne Mofenson, Philippa Musoke, Sharon Nachman, Clydette Powell, Mona Rigaud, Vanessa Rouzier, Jeffrey R. Starke, Soumya Swaminathan and Claire Wingfield

New Reference standards for TB diagnostics in children

As has been highlighted on World TB day, children with TB are an neglected population usually omitted from research in treatment and diagnostics. Accurate diagnosis of Mycobacterium tuberculosis in children has long been difficult and current diagnostic tools available fail to address the problems experienced in diagnosing TB in children. The development of new tools for children has been hampered by a lack of consensus on case definitions for research purposes. A lack of reference standard contributes to the hesitancy to enrol children in diagnostic research studies. Research into paediatric TB diagnostics is very limited and a consensus on a reference standard should promote further research and ensure that the maximum benefits can be gained from it.

The National Institute of Health sponsored a meeting in June last year “Critical Issues in Paediatric Tuberculosis Diagnostics Research in HIV-Infected and Uninfected Children” bringing together a group of leading paediatric TB experts. The meeting addressed the lack of an agreed  reference standard for diagnostics and a expert consensus was reached on clinical case definitions for intra-thoracic TB diagnosis in children, as well as how to standardize methodological approaches for evaluation of new TB diagnostic tests in children which was published this month in Journal of Infectious Diseases. The published document clearly specifies how to use their definitions to reliably classify a child for research purposes. 


There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis.

A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement.

The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.