Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts.
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
JAMA Pediatr. 2021 May 1;175(5):e206069. doi: 10.1001/jamapediatrics.2020.6069. Epub 2021 May 3.
Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify.
To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined.
DESIGN, SETTING, AND PARTICIPANTS: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020.
Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield.
Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31).
NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.
在资源有限的环境中，用于儿童结核病诊断的标准标本（胃液抽吸物[GA]和诱导痰）具有侵袭性，很少采集。开发一种比目前参考标准更敏感的用于 5 岁以下儿童结核病诊断测试的侵入性更小的方法非常重要，以便能够识别结核病。
描述首选微创标本和检测组合相对于所有标本和检测组合最大观察到的产量的灵敏度。
设计、地点和参与者：在这项前瞻性横断面诊断研究中，参考标准是一个由最多 6 种标本类型的每个标本的 2 个样本组成的面板，这些标本均通过 Xpert MTB/RIF 检测和分枝杆菌生长指示管培养来检测结核分枝杆菌复合体。评估了多种不同的标本和检测组合作为指标检测。2013 年 10 月至 2015 年 8 月，在肯尼亚基苏木县的住院和门诊环境中连续招募了一系列儿童。参与者是有结核病症状（无原因咳嗽、发热、营养不良）和胸部 X 线片上有实质异常或有颈部淋巴结病的 5 岁以下儿童。有 4 种或更多种主要研究标本的 1 种或多种可评估标本的儿童纳入分析。数据于 2015 年 2 月至 2020 年 10 月进行分析。
相对于最大观察到的产量，标本类型和检测组合的累积和增量诊断产量。
在 300 名入组的儿童中，中位数（四分位距）年龄为 2.0（1.0-3.6）岁，151 名（50.3%）为女性。共有 294 名符合分析标准。在 31 名确诊结核病的参与者（最大观察到的产量）中，24 名（灵敏度，77%；十分位数范围，68%-87%）的 2 份 GA 样本检测结果为阳性，20 名（灵敏度，64%；十分位数范围，53%-76%）的 2 份诱导痰样本检测结果为阳性。2 份鼻咽抽吸物（NPA）样本（31 份中 23 份[灵敏度，74%；十分位数范围，64%-84%]）、1 份 NPA 样本和 1 份粪便样本（31 份中 22 份[灵敏度，71%；十分位数范围，60%-81%]）或 1 份 NPA 样本和 1 份尿液样本（31 份中 21.5 份[灵敏度，69%；十分位数范围，58%-80%]）的产量与参考标准标本相似。每份 GA 和 NPA 样本各 2 份的组合平均产量为 90%（31 份中有 28 份）。
NPA 重复检测或与粪便或尿液标本联合检测，容易获得，且诊断产量与参考标准标本相当。这种组合可以提高资源有限环境中儿童的结核病诊断率。GA 和 NPA 的联合使用比目前的参考标准具有更高的产量，在某些临床和研究环境中可能有用。
