The diagnostics platform within the DTTC paediatric research programme


The diagnostics platform within the DTTC paediatric research programme

The diagnosis of TB in young children can be challenging and is seldom bacteriologically confirmed, as young children, who are most affected by the disease, cannot produce sputum spontaneously. In order to obtain adequate specimens for lab testing, relatively invasive methods are used. In addition, the current gold standard of diagnosis, TB culture, detects only approximately 30% of children treated for TB. Culture results take up to 6 weeks in children, who typically have paucibacillary TB (low organism load). In resource-limited settings, capacity for respiratory sampling of young children, in terms of both human resources and equipment, is typically low.

These challenges result in poor estimations of the true global burden of paediatric TB. Diagnostic uncertainty also compromises the clinical management of children with TB, as it may result in over- and under-treatment.

Although a number of new rapid diagnostic tests has recently become available, the majority of these tests are aimed at adults rather than children. It is clear that the correct diagnosis of children in whom TB is suspected, requires not only improved tests but rather comprehensive strategies that are feasible to implement at the levels of health care where such children present.

The primary focus of the current diagnostic studies conducted at DTTC is the development of novel and comprehensive strategies to improve the diagnosis of pulmonary TB in children, focusing on child-friendly and high-quality specimen collection.  Children who present to hospital with symptoms of possible pulmonary TB undergo intensive investigation which includes the collection of multiple respiratory samples, stool and urine. Important clinical data are collected and all children are followed up for 6 months regardless of final diagnosis. Some of the novel strategies under investigation include pooling same-day respiratory samples prior to analysis by culture and Xpert, optimized concentration and decontamination methods at the lab, and analyzing stool samples using a different molecular platforms including GeneXpert.

Our group has disseminated results on the utility of stool for TB diagnosis in children (1, 2) and optimization of this approach is ongoing. We are also building a bio-repository of urine and blood samples for future biomarker studies.

Principal Investigator: Dr Liz Walters:

  1. Walters E, Gie RP, Hesseling AC, Friedrich SO, Diacon AH. Rapid Diagnosis of Pediatric Intrathoracic Tuberculosis From Stool Samples Using the Xpert MTB/RIF Assay: A Pilot Study. Pediatr Infect Dis J. 2012;31(12):1316. Epub 2012/11/29. doi: 10.1097/INF.0b013e318266c21c00006454-201212000-00029 [pii]. PubMed PMID: 23188101.
  2. Walters E, Bosch C, van der Zalm M, Friedrich SO, Gie RP, Hesseling AC. The value of stool for the diagnosis of intrathoracic tuberculosis in children. 45th Union World Conference on Lung Health; Bracelona, Spain 2014.