一种新型粪便定量聚合酶链反应检测法在撒哈拉以南非洲地区儿童结核病检测中的性能评估

Performance of a Novel Stool Quantitative Polymerase Chain Reaction Assay for Pediatric Tuberculosis Detection in Sub-Saharan Africa.

作者信息

Vasiliu Anca, Carratala-Castro Lucia, Seeger Abigail, Ehrlich Joanna, Nkala Babongile, Ness Tara, Cumbe Miguel Mario, Mulengwa Durbbin, Munguambe Shilzia, Mtafya Bariki, Mambuque Edson, Shiba Nosisa, Acacio Sozinho, Komba Lilian, Adu-Gyamfi Clement Gascua, Kirchner H Lester, Lange Christoph, DiNardo Andrew R, Garcia-Basteiro Alberto L, Mandalakas Anna Maria, Kay Alexander

机构信息

Baylor College of Medicine, Department of Pediatrics, Global TB Program, Houston, TX 77030, United States.

Research Center Borstel, Division of Clinical Infectious Diseases, Borstel, Germany.

出版信息

J Pediatric Infect Dis Soc. 2025 Jun 16;14(6). doi: 10.1093/jpids/piaf045.

DOI:10.1093/jpids/piaf045

PMID:40391711

Abstract

BACKGROUND

Children have paucibacillary tuberculosis and cannot provide expectorated sputum. Invasive specimen collection, by gastric aspiration or sputum induction, has a low diagnostic yield. In this study, we aimed to evaluate the diagnostic performance and additive yield of a novel stool-based assay in children diagnosed with tuberculosis in sub-Saharan Africa.

METHODS

We conducted a prospective case-control study from October 2020 to June 2023 in Eswatini, Mozambique, and Tanzania. Children under 15 years newly diagnosed with tuberculosis completed clinical examination, chest radiography, culture, sputum Xpert Ultra, stool Xpert Ultra, and stool-based quantitative polymerase chain reaction (stool qPCR) assessment. Stool qPCR sensitivity was calculated against culture, a composite microbiological reference standard, and a clinical reference standard. Specificity was calculated in a control population of healthy, TB disease-free, child household contacts.

RESULTS

Among 456 children, 232 were diagnosed with TB and 224 controls. Stool sample collection was achieved in 95.6% of children. The qPCR was positive in 17.2% (40/232) of clinically diagnosed participants. In the same population, test positivity was 8% (13/162) for culture, 13.4% (27/202) sputum Xpert Ultra, and 14.8% (33/223) stool Xpert Ultra. When compared to a microbiological reference standard (any positive test), the sensitivity of stool qPCR was 35.6% (21/59). Specificity in the control population was 96.1% (196/204), and the additive yield of qPCR with all tests performed was of 8.7%.

CONCLUSION

This stool qPCR assay can increase the microbiologic confirmation of tuberculosis in pediatric populations from TB high-burden settings. It may be particularly useful where resource limitations or clinical capacity impedes diagnostic specimen collection via sputum induction or gastric aspiration.

摘要

背景

儿童患少菌型肺结核，无法咳出痰液。通过胃抽吸或诱导咳痰进行侵入性标本采集的诊断阳性率较低。在本研究中，我们旨在评估一种新型粪便检测方法在撒哈拉以南非洲地区被诊断为结核病的儿童中的诊断性能和附加阳性率。

方法

2020年10月至2023年6月，我们在斯威士兰、莫桑比克和坦桑尼亚进行了一项前瞻性病例对照研究。新诊断为结核病的15岁以下儿童完成了临床检查、胸部X光检查、培养、痰液Xpert Ultra检测、粪便Xpert Ultra检测和基于粪便的定量聚合酶链反应（粪便qPCR）评估。针对培养（一种综合微生物学参考标准）和临床参考标准计算粪便qPCR的敏感性。在健康、无结核病的儿童家庭接触者对照人群中计算特异性。

结果

456名儿童中，232名被诊断为结核病，224名作为对照。95.6%的儿童成功采集了粪便样本。在临床诊断的参与者中，qPCR阳性率为17.2%（40/232）。在同一人群中，培养的检测阳性率为8%（13/162），痰液Xpert Ultra为13.4%（27/202），粪便Xpert Ultra为14.8%（33/223）。与微生物学参考标准（任何阳性检测）相比，粪便qPCR的敏感性为35.6%（21/59）。对照人群中的特异性为96.1%（196/204），进行所有检测时qPCR的附加阳性率为8.7%。