Khambati Nisreen, Olbrich Laura, Ellner Jerrold, Salgame Padmini, Song Rinn, Bijker Else Margreet
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
Front Pediatr. 2021 Oct 25;9:756043. doi: 10.3389/fped.2021.756043. eCollection 2021.
The diagnosis of pulmonary tuberculosis (TB) in children remains a significant challenge due to its paucibacillary nature, non-specificity of symptoms and suboptimal sensitivity of available diagnostic methods. In young children particularly, it is difficult to obtain high-quality sputum specimens for testing, with this group the least likely to be diagnosed, while most at risk of severe disease. The World Health Organization (WHO) has prioritized research into rapid biomarker-based tests for TB using easily obtainable non-sputum samples, such as saliva. However, the role of biomarkers in saliva for diagnosing TB in children has not been fully explored. In this mini-review, we discuss the value of saliva as a diagnostic specimen in children given its ready availability and non-invasive nature of collection, and review the literature on the use of host-based biomarkers in saliva for diagnosing active pulmonary TB in adults and children. Based on available data from adult studies, we highlight that combinations of cytokines and other proteins show promise in reaching WHO-endorsed target product profiles for new TB triage tests. Given the lack of pediatric research on host biomarkers in saliva and the differing immune response to TB infection between children and adults, we recommend that pediatric studies are now performed to discover and validate salivary host biosignatures for diagnosing pulmonary TB in children. Future directions for pediatric saliva studies are discussed, with suggestions for technologies that can be applied for salivary biomarker discovery and point-of-care test development.
由于儿童肺结核（TB）菌量少、症状不具特异性且现有诊断方法的敏感性欠佳，其诊断仍然是一项重大挑战。特别是在幼儿中，很难获取高质量的痰液标本进行检测，这一群体最不容易被诊断出来，但患重症的风险却最高。世界卫生组织（WHO）已将利用易于获取的非痰液样本（如唾液）开展基于快速生物标志物的结核病检测研究列为优先事项。然而，唾液中的生物标志物在儿童结核病诊断中的作用尚未得到充分探索。在这篇小型综述中，我们鉴于唾液易于获取且采集无创，讨论了其作为儿童诊断标本的价值，并回顾了关于利用唾液中基于宿主的生物标志物诊断成人和儿童活动性肺结核的文献。基于成人研究的现有数据，我们强调细胞因子和其他蛋白质的组合有望达到WHO认可的新型结核病分流检测目标产品标准。鉴于缺乏关于唾液中宿主生物标志物的儿科研究，以及儿童和成人对结核菌感染的免疫反应不同，我们建议现在开展儿科研究，以发现和验证用于诊断儿童肺结核的唾液宿主生物特征。文中讨论了儿科唾液研究的未来方向，并对可用于唾液生物标志物发现和即时检测开发的技术提出了建议。
