Ssengooba Willy, Iragena Jean de Dieu, Nakiyingi Lydia, Mujumbi Serestine, Wobudeya Eric, Mboizi Robert, Boulware David, Meya David B, Choo Louise, Crook Angela M, Lebeau Kristen, Joloba Moses, Demers Anne-Marie, Cresswell Fiona V, Gibb Diana M
Makerere University, Department of Medical Microbiology, Mycobacteriology (BSL-3) Laboratory, Kampala, Uganda
Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.
J Clin Microbiol. 2020 Aug 24;58(9). doi: 10.1128/JCM.00410-20.
Childhood tuberculosis (TB) presents significant diagnostic challenges associated with paucibacillary disease and requires a more sensitive test. We evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Ultra) compared to other microbiological tests using respiratory samples from Ugandan children in the SHINE trial. SHINE is a randomized trial evaluating shorter treatment in 1,204 children with minimal TB disease in Africa and India. Among 352 samples and one cervical lymph node fine needle aspirate, one sample was randomly selected per patient and tested with the Xpert MTB/RIF assay (Xpert) and with Lowenstein-Jensen medium (LJ) and liquid mycobacterial growth indicator tube (MGIT) cultures. We selected only uncontaminated stored sample pellets for Ultra testing. We estimated the sensitivity of Xpert and Ultra against culture and a composite microbiological reference standard (any positive result). Of 398 children, 353 (89%) had culture, Xpert, and Ultra results. The median age was 2.8 years (interquartile range [IQR], 1.3 to 5.3); 8.5% (30/353) were HIV infected, and 54.4% (192/353) were male. Of the 353, 31 (9%) were positive by LJ and/or MGIT culture, 36 (10%) by Ultra, and 16 (5%) by Xpert. Sensitivities (95% confidence intervals [CI]) were 58% (39 to 65% [18/31]) for Ultra and 45% (27 to 64% [14/31]) for Xpert against any culture-positive result, with false positives of <1% and 5.5% for Xpert and Ultra. Against a composite microbiological reference, sensitivities were 72% (58 to 84% [36/50]) for Ultra and 32% (20 to 47% [16/50]) for Xpert. However, there were 17 samples that were positive only with Ultra (majority trace). Among children screened for minimal TB in Uganda, Ultra has higher sensitivity than Xpert. This represents an important advance for a condition which has posed a diagnostic challenge for decades.
儿童结核病在诊断上面临着与少菌型疾病相关的重大挑战，需要一种更灵敏的检测方法。在“SHINE试验”中，我们使用乌干达儿童的呼吸道样本，评估了Xpert MTB/RIF Ultra（Ultra）与其他微生物检测方法相比的诊断准确性。“SHINE试验”是一项随机试验，旨在评估非洲和印度1204名患有轻度结核病的儿童接受更短疗程治疗的效果。在352份样本和1份颈淋巴结细针穿刺抽吸物中，为每位患者随机选取1份样本，采用Xpert MTB/RIF检测法（Xpert）、洛温斯坦-詹森培养基（LJ）和液体分枝杆菌生长指示管（MGIT）培养法进行检测。我们仅选择未受污染的储存样本沉淀用于Ultra检测。我们评估了Xpert和Ultra相对于培养法以及综合微生物学参考标准（任何阳性结果）的敏感性。在398名儿童中，353名（89%）有培养、Xpert和Ultra检测结果。中位年龄为2.8岁（四分位间距[IQR]，1.3至5.3岁）；8.5%（30/353）感染了HIV，54.4%（192/353）为男性。在这353名儿童中，31名（9%）LJ和/或MGIT培养呈阳性，36名（10%）Ultra检测呈阳性，16名（5%）Xpert检测呈阳性。相对于任何培养阳性结果，Ultra的敏感性（95%置信区间[CI]）为58%（39%至65%[18/31]），Xpert为45%（27%至64%[14/31]），Xpert和Ultra的假阳性率分别为<1%和5.5%。相对于综合微生物学参考标准，Ultra的敏感性为72%（58%至84%[36/50]），Xpert为32%（20%至47%[16/50]）。然而，有17份样本仅Ultra检测呈阳性（大多数为痕量）。在乌干达筛查轻度结核病的儿童中；Ultra比Xpert具有更高的敏感性。对于一个数十年来一直构成诊断挑战的疾病来说，这是一项重要进展。
