Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary

Abstract

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.

Diagnostic accuracy of Xpert MTB/RIF ultra for detection of Mycobacterium tuberculosis in children: a prospective cohort study

“…The highest global burden of pediatric TB is in Africa and South East Asia (Global Tuberculosis Report 2019). Most pediatric deaths related to TB are seen in those not receiving anti-TB therapy, emphasizing the difficulty in the diagnosis (Atherton et al 2019).…”

Diagnostic utility of bronchoalveolar lavage in children with complicated intrathoracic tuberculosis

“…We can hypothesize, however, that the diagnostic yield using Ultra would be at least as high as what was achieved by Xpert, given the higher sensitivity of Ultra. 20 We analyzed data from a tertiary hospital in a high TB-endemic area, and we believe that our results can still inform practice in this setting. Finally, the group included in this study is a highly select cohort with a high pretest probability of TB.…”

Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa

“…There is very limited evidence to inform accurate screening strategies to support active TB case finding in CALHIV. Future research is needed to assess the utility of TB screening strategies in CALHIV that build off symptom screening by including novel strategies, such as blood C-reactive protein [ 5 ], automated chest radiograph interpretation algorithms [ 20 ], and microbiologic assays that rely on easily obtained specimens, such as urine or stool [ 21 , 22 ].…”