The publication, entitled “Contribution of Xpert© MTB/Rif to the diagnosis of pulmonary tuberculosis among TB-exposed children in The Gambia”, is scheduled to appear in the September issue of The International Journal of Tuberculosis and Lung Disease, which is the official publication of the International Union Against Tuberculosis and Lung Disease (The Union).
This is the very first study to report the diagnostic accuracy and added value of the GeneXpert© MTB/Rif assay (Xpert) in an active case-finding study setting among an exclusively paediatric population of TB contacts in a low-income country. The Xpert is a WHO endorsed rapid diagnostic device (WRD) for the rapid diagnosis of TB and Rifampicin resistance, which is currently being scaled up in many high TB burden settings. The research work contained in this publication is part of the MRC-funded Clinical PhD Training Fellowship awarded to Dr. Toyin Omotayo Togun who is the first author of the publication. His research work is nested within the MRC Childhood TB Program Grant to Professor Beate Kampmann, which is supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and the WHO STOP TB/TBReach Wave 2 Grant.

The overall aim of the PhD research study is to improve the diagnosis of TB in children using an immuno-epidemiological approach, however one of the specific objectives is to investigate the diagnostic accuracy of Xpert in TB-exposed children with suspected intrathoracic TB. The study reported that the sensitivity of Xpert, which is known to be lower in children than in adults, is even much lower in ambulant populations such as actively traced child contacts, than in children in hospital based studies. The study further reported that Xpert and Mycobacterium tuberculosis (M.tb) culture methods detected a comparable number of TB cases among all children diagnosed with active TB disease, although both solid and liquid M.tb culture methods are known to have sub-optimal sensitivity in children. The findings from the study support the notion that culture of respiratory specimens is still advisable in children if it is available because, unlike sputum smear microscopy, it has incremental benefits when combined with Xpert testing.

An estimated half a million children aged <15 years become ill with TB every year resulting in up to 70 000 deaths, however the true burden of TB in children remains unknown principally because of difficulties with the diagnosis of TB in children. In 2010, the Xpert was endorsed by the WHO for the rapid diagnosis of pulmonary TB based mostly on data from several large adult studies. However, data on its diagnostic accuracy in children are still emerging. Children exposed to adults with sputum smear positive TB have a very high likelihood of developing active TB themselves, and should be investigated for TB. While such screening of child TB contacts is recommended by the WHO, it is rarely performed in resource-constrained high TB burden countries. This particular study finding of a very low sensitivity of the Xpert in ambulant populations of TB-exposed children has strong implications for its use as a diagnostic tool for TB among children in this context, especially given the emerging concerns about the feasibility and cost-effectiveness of decentralised Xpert testing in high TB burden settings.

With the funding support as stated above, the MRC childhood TB program in collaboration with the National Leprosy and TB Control Programme of The Gambia (NLTP) have established a large prospective community based cohort of children with documented history of exposure to an infectious TB case, which has provided an epidemiological platform for clinical, epidemiological and hypothesis-driven laboratory research studies.

The first author, Dr Toyin Omotayo Togun, MRC-Clinical Research Training Fellow Said: “This study suggest that the relatively new Xpert is not the “silver bullet” for diagnosis of TB, particularly in children at the primary care settings where majority of adults and children with suspected intrathoracic TB are likely to be seen first and where diagnosis is likely to be missed with negative consequences. The fact that an overwhelming majority of children that are started on TB treatment do not have microbiological confirmation of disease reinforce the need for further research to identify new diagnostic tools for fast and accurate classification of TB in children and other subjects with paucibacillary disease. We are currently exploring the use of host-specific immunological tools for this.”