Atherton Rachel R, Cresswell Fiona V, Ellis Jayne, Kitaka Sabrina B, Boulware David R
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Front Pediatr. 2019 Feb 28;7:34. doi: 10.3389/fped.2019.00034. eCollection 2019.
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 ; 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.
结核病（TB）仍是儿科人群中一个重要但未得到充分认识的死亡原因，据世界卫生组织估计，2016年有100万例儿童新发结核病病例，导致25万人死亡。众所周知，结核病的诊断很困难；由于儿童肺外结核病病例比例很高，其表现形式多样，而且在获取合适标本方面存在后勤问题。疾病的少菌性使这些问题更加复杂，结果是估计96%的儿童结核病相关死亡发生在开始抗结核治疗之前。在这一人群中，进一步开发敏感、快速的诊断测试并将其纳入诊断算法至关重要，这也是世界卫生组织终止结核病战略的核心。随着核酸扩增技术的扩展取得了初步进展，特别是2010年引入了GeneXpert全自动PCR Xpert MTB/Rif检测，以及最近在2017年引入了Xpert MTB/Rif Ultra（Ultra）检测。与最初的Xpert检测相比，Ultra提供了更高的分析灵敏度；迄今为止的六项临床研究也支持了这一发现，其中两项研究包括儿科样本。在此，我们回顾了已发表的关于Ultra在儿童结核病诊断中性能的证据，以及在少菌性疾病成人中的研究结果，这些结果与儿科人群相关。在此基础上，我们推测了Ultra的未来发展方向，重点是其与替代诊断标本的潜在用途，这在儿童中可能特别有用。
