Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro ; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children.

BackgroundClinical application of body composition (BC) measurements for individual children has been limited by lack of appropriate reference data.Objectives(1) To compare fat mass (FM) and fat free mass (FFM) standard deviation scores (SDS) generated using new body composition reference data and obtained using simple measurement methods in healthy children and patients with those obtained using the reference 4-component (4-C) model; (2) To determine the extent to which scores from simple methods agree with those from the 4-C model in identification of abnormal body composition.DesignFM SDS were calculated for 4-C model, dual-energy X-ray absorptiometry (DXA; GE Lunar Prodigy), BMI and skinfold thicknesses (SFT); and FFM SDS for 4CM, DXA and bioelectrical impedance analysis (BIA; height2/Z)) in 927 subjects aged 3.8–22.0 y (211 healthy, 716 patients).ResultsDXA was the most accurate method for both FM and FFM SDS in healthy subjects and patients (mean bias (limits of agreement) FM SDS 0.03 (±0.62); FFM SDS −0.04 (±0.72)), and provided best agreement with the 4-C model in identifying abnormal BC (SDS ≤−2 or ≥2). BMI and SFTs were reasonable predictors of abnormal FM SDS, but poor in providing an absolute value. BIA was comparable to DXA for FFM SDS and in identifying abnormal subjects.ConclusionsDXA may be used both for research and clinically to determine FM and FFM SDS. BIA may be used to assess FFM SDS in place of DXA. BMI and SFTs can be used to measure adiposity for groups but not individuals. The performance of simpler techniques in monitoring longitudinal BC changes requires investigation. Ultimately, the most appropriate method should be determined by its predictive value for clinical outcome.

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HighlightsUltra has detected Mycobacterium tuberculosis in the urine of a patient with renal TB.Use of Xpert or Ultra on urine is not currently recommended due to lack of evidence.Urine Ultra may be useful in the diagnosis of extra-pulmonary TB in persons with HIV.Further study is required to characterise the diagnostic accuracy of urine Ultra.