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新生儿和婴儿的无创性脑膜炎筛查:多中心国际研究

Non-invasive meningitis screening in neonates and infants: multicentre international study.

作者信息

Ajanovic Sara, Jobst Beatrice, Jiménez Javier, Quesada Rita, Santos Fabião, Carandell Francesc, Lopez-Azorín Manuela, Valverde Eva, Ybarra Marta, Bravo María Carmen, Petrone Paula, Sial Hassan, Muñoz David, Agut Thais, Salas Barbara, Carreras Nuria, Alarcón Ana, Iriondo Martín, Luaces Carles, Sidat Muhammad, Zandamela Mastalina, Rodrigues Paula, Graça Dulce, Ngovene Sebastião, Bramugy Justina, Cossa Anelsio, Mucasse Campos, Buck William Chris, Arias Sara, El Abbass Chaymae, Tligi Houssain, Barkat Amina, Ibáñez Alberto, Parrilla Montserrat, Elvira Luis, Calvo Cristina, Pellicer Adelina, Cabañas Fernando, Bassat Quique

机构信息

ISGlobal, Barcelona, Spain.

Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.

出版信息

Pediatr Res. 2025 Jul 23. doi: 10.1038/s41390-025-04179-7.

Abstract

BACKGROUND AND OBJECTIVES

Meningitis diagnosis requires a lumbar puncture (LP) to obtain cerebrospinal fluid (CSF) for a laboratory-based analysis. In high-income settings, LPs are part of the systematic approach to screen for meningitis, and most yield negative results. In low- and middle-income settings, LPs are seldom performed, and suspected cases are often treated empirically. The aim of this study was to validate a non-invasive transfontanellar white blood cell (WBC) counter in CSF to screen for meningitis.

METHODS

We conducted a prospective study across three Spanish hospitals, one Mozambican and one Moroccan hospital (2020-2023). We included patients under 24 months with suspected meningitis, an open fontanelle, and a LP performed within 24 h from recruitment. High-resolution-ultrasound (HRUS) images of the CSF were obtained using a customized probe. A deep-learning model was trained to classify CSF patterns based on LPs WBC counts, using a 30cells/mm threshold.

RESULTS

The algorithm was applied to 3782 images from 76 patients. It correctly classified 17/18 CSFs with 30 WBC, and 55/58 controls (sensitivity 94.4%, specificity 94.8%). The only false negative was paired to a traumatic LP with 40 corrected WBC/mm.

CONCLUSIONS

This non-invasive device could be an accurate tool for screening meningitis in neonates and young infants, modulating LP indications.

IMPACT

Our non-invasive, high-resolution ultrasound device achieved 94% accuracy in detecting elevated leukocyte counts in neonates and infants with suspected meningitis, compared to the gold standard (lumbar punctures and laboratory analysis). This first-in-class screening device introduces the first non-invasive method for neonatal and infant meningitis screening, potentially modulating lumbar puncture indications. This technology could substantially reduce lumbar punctures in low-suspicion cases and provides a viable alternative critically ill patients worldwide or in settings where lumbar punctures are unfeasible, especially in low-income countries).

摘要

背景与目的

脑膜炎的诊断需要进行腰椎穿刺(LP)以获取脑脊液(CSF)用于实验室分析。在高收入地区,腰椎穿刺是筛查脑膜炎系统方法的一部分,且大多数结果为阴性。在低收入和中等收入地区,很少进行腰椎穿刺,疑似病例通常凭经验治疗。本研究的目的是验证一种用于脑脊液的无创经囟门白细胞(WBC)计数仪以筛查脑膜炎。

方法

我们在三家西班牙医院、一家莫桑比克医院和一家摩洛哥医院开展了一项前瞻性研究(2020 - 2023年)。我们纳入了年龄在24个月以下、疑似脑膜炎、囟门未闭且在招募后24小时内进行了腰椎穿刺的患者。使用定制探头获取脑脊液的高分辨率超声(HRUS)图像。基于腰椎穿刺白细胞计数,使用30个细胞/立方毫米的阈值,训练一个深度学习模型来对脑脊液模式进行分类。

结果

该算法应用于76例患者的3782张图像。它正确分类了17/18例白细胞计数≥30的脑脊液,以及55/58例对照(敏感性94.4%,特异性94.8%)。唯一的假阴性与一次创伤性腰椎穿刺相关,校正后的白细胞计数为40/立方毫米。

结论

这种无创设备可能是一种准确的工具,用于筛查新生儿和幼儿的脑膜炎,从而调整腰椎穿刺的指征。

影响

与金标准(腰椎穿刺和实验室分析)相比,我们的无创高分辨率超声设备在检测疑似脑膜炎的新生儿和婴儿白细胞计数升高方面准确率达到94%。这种一流的筛查设备引入了第一种用于新生儿和婴儿脑膜炎筛查的无创方法,有可能调整腰椎穿刺指征。这项技术可以大幅减少低怀疑度病例的腰椎穿刺次数,并为全球危重症患者或在腰椎穿刺不可行的地区,特别是低收入国家,提供一种可行的替代方法。

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