No added value of interferon-gamma release to a prediction model for childhood tuberculosis.

A new publication from The Unit’s childhood tuberculosis (TB) research project (Reach-4-Kids; ‘R4K’) will be published online by the European Respiratory Journal (ERJ) on October 22 2015, ahead of print in the January 2016 issue. This study, titled “No added Value of Interferon-gamma release to a Prediction Model for Childhood Tuberculosis”, is one of the outputs from Dr Toyin Togun’s MRC-funded PhD fellowship nested within the childhood TB research group of the Vaccines and Immunity theme led by Professor Beate Kampmann.

The authors report that interferon (IFN)-gamma release assay (IGRAs) does not add any further incremental value to the discriminatory ability of a clinical prediction model, which includes the combination of ‘age less than 5 years’ and presence of ‘lymphadenopathy’ on clinical examination. This very simple algorithm reliably distinguished at least 70% of TB disease from other respiratory tract infections among TB-exposed children with suspected intrathoracic TB, and could select child-contacts with high or low risk of TB disease with positive and negative predictive values of at least 80%.

Diagnosis of TB disease in children remains a major challenge despite the recent advances, including introduction of new microbiological and molecular tools for the diagnosis of TB. An integrated approach, which entails combining clinical and epidemiological data with host and pathogen signature, has been suggested for all areas of TB research, including investigation and development of new diagnostics. The utility of IGRAs when used as an adjunct test in combination with clinical, radiological and microbiological parameters, remain an important area of knowledge gap, but data are generally sparse on the utility of T-cell based assays among children in resource-limited TB endemic settings. This paper, in which the authors developed an optimal multivariable risk prediction model for TB disease among symptomatic TB-exposed children, is the first study to investigate and report the utility of IGRAs in a multivariable algorithm for co-prevalent TB disease when applied in an exclusively paediatric active contact tracing study setting.

Dr Toyin TogunDr Toyin Togun, the first-author of this publication said “our most important message from this paper is that, by using robust statistical methods, we identified a very simple clinical algorithm that could predict TB disease with good accuracy in symptomatic TB-exposed children and is potentially an effective screening tool for the purpose of risk stratification. This clinical algorithm could result in earlier diagnosis and treatment of childhood TB in general, but it is even more important and useful in the context of the WHO-recommended provision of isoniazid prophylaxis for all TB contacts aged less than 5 years, where there is the crucial need to rule out TB disease first. Efforts are ongoing to validate this algorithm in a different setting and population”.

This publication will be published online, on the European Respiratory Journal (ERJ)  website on October 22nd  2015, ahead of the January 2016 issue.