Validation of host blood RNA signatures for paediatric Tuberculosis
Ashleigh Cheyne1, Ortensia Vito2, Lesley Workman3, Giselle D’Souza2, Victoria Wright2, Sandra Newton2, Mark Nicol4, Heather Zar3, Michael Levin2, and Myrsini Kaforou2
MRC Centre for Molecular Bacteriology and Infection, Imperial College London1
Department of Infectious Disease, Faculty of Medicine, Imperial College London2
Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town3
Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia4
Tuberculosis is the leading cause of death from an infection disease worldwide, in part due to the lack of an effective diagnostic test. Several tests have been developed, including culturing Mycobacterium tuberculosis which is the current gold standard. All tests have their limitations, and all prove ineffective in children due to the nature of the disease. As a result, in recent years whole blood transcriptomic signatures with diagnostic potential have been identified as an alternative method, which can differentiate tuberculosis patients from controls. While some of these signatures have shown high specificity and sensitivity, studies are restricted by several factors including deriving signatures from a patient cohort from a single country which may be ineffective on individuals from different populations. In this study, we validate previously published signatures from both adult and paediatric cohorts in an independent dataset of paediatric tuberculosis patients from South Africa. Furthermore, we compare these signatures with the current WHO requirements for developing new tuberculosis diagnostic test and identify which, if any, signatures meet these requirements.