Improving the Diagnosis of Childhood Tuberculosis in High Burden Settings

In 2014, there were an estimated 1 million incident cases of tuberculosis (TB) in children younger than 15 years of age, while as many as 140,000 children died of TB. About 75% of all childhood TB cases occur every year in the 22 high burden countries, most of which are in sub-Sahara Africa. Differentiating TB from other respiratory diseases (ODs) in children with suspected TB disease is difficult, especially if diagnosis relies on clinical and radiological features or microbiological assays, since children often cannot produce sputum. In this project, we propose to validate a novel multi-cytokine diagnostic biosignature identified in HIV-negative children previously, to distinguish TB disease from ODs among childhood populations, including children under 5 years old, with a different HIV and TB epidemiology in Malawi and The Gambia. This project will use archived whole blood assay plasma supernatants (unstimulated, positive control and antigen stimulated samples) and ex-vivo plasma samples obtained from a prospective cohort of children with suspected intrathoracic TB, recruited in Malawi (south-eastern Africa) and The Gambia (West Africa) prior to initiation of specific anti-TB treatment. We will carry out a comprehensive multiplex cytokine analysis of the samples by Luminex at the Medical Research Council Unit The Gambia (MRCG). This biosignature has potential to be developed into a non-sputum-based point-of-care (POC) test, which is a felt need in the field of TB.