Department of Biochemistry and Molecular Biology Center for Cellular and Molecular Diagnosis, School of Medicine, Tulane University, New Orleans, Louisiana, USA.
Shanghai Clinical Research Center for Infectious Diseases (Tuberculosis), Shanghai, China.
J Clin Microbiol. 2021 Jan 21;59(2). doi: 10.1128/JCM.01756-20.
Diagnosis of pediatric tuberculosis (TB) is often complicated by its nonspecific symptoms, paucibacillary nature, and the need for invasive specimen collection techniques. However, a recently reported assay that detects virulence factors in serum can diagnose various TB manifestations, including paucibacillary TB cases, in adults with good sensitivity and specificity. The current study examined the ability of this biomarker assay to diagnose pediatric TB using archived cryopreserved serum samples drawn from children ≤18 years of age who were screened for suspected TB as part of a prospective population-based active surveillance study. In this analysis, any detectable level of either of the virulence factors CFP-10 and ESAT-6 was considered direct evidence of TB. Serum samples from 105 children evaluated for TB (55 TB cases and 50 close contacts without TB) were analyzed. The results of this analysis yielded sensitivity of 85.5% (95% confidence interval [CI], 73.3 to 93.5). Similar diagnostic sensitivities were observed for culture-positive (87.5%; 95% CI, 67.6 to 97.3) and culture-negative (83.9%; 95% CI, 66.3 to 94.5) TB cases and for culture negative pulmonary (77.8%; 95% CI, 40.0 to 97.2) and extrapulmonary (86.4%; 95% CI, 65.1 to 97.1) TB cases. These results suggest that serum biomarker analysis holds significant promise for rapid and sensitive diagnosis of pediatric TB cases, including extrapulmonary or paucibacillary TB cases. The ability to use frozen samples for this analysis should also permit assays to be performed at central sites, without a requirement for strict timelines for sample analysis.
诊断小儿结核病 (TB) 常常因其非特异性症状、菌量少和需要侵入性标本采集技术而变得复杂。然而，最近报道的一种检测血清中毒力因子的检测方法可以诊断各种结核病表现，包括菌量少的结核病病例，在成人中具有良好的敏感性和特异性。本研究使用存档的冷冻血清样本检测了该生物标志物检测方法在作为前瞻性基于人群的主动监测研究一部分筛查疑似结核病的儿童中诊断小儿结核病的能力。在该分析中，任何可检测到的毒力因子 CFP-10 和 ESAT-6 的水平均被认为是结核病的直接证据。对 105 名疑似结核病儿童的血清样本（55 例结核病病例和 50 名无结核病的密切接触者）进行了分析。该分析的结果得出了 85.5%（95%置信区间 [CI]，73.3 至 93.5）的敏感性。在培养阳性（87.5%；95%CI，67.6 至 97.3）和培养阴性（83.9%；95%CI，66.3 至 94.5）结核病病例以及培养阴性肺部（77.8%；95%CI，40.0 至 97.2）和肺外（86.4%；95%CI，65.1 至 97.1）结核病病例中观察到类似的诊断敏感性。这些结果表明，血清生物标志物分析在快速和敏感地诊断小儿结核病病例方面具有重要意义，包括肺外或菌量少的结核病病例。该分析中使用冷冻样本的能力还应允许在中央站点进行检测，而无需严格的样本分析时间限制。
