Non-invasive meningitis screening in neonates and infants: multicentre international study.
Authors
Affiliations (27)
Affiliations (27)
- ISGlobal, Barcelona, Spain. [email protected].
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain. [email protected].
- Kriba, Barcelona Science Park, Barcelona, Spain. [email protected].
- Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique. [email protected].
- Kriba, Barcelona Science Park, Barcelona, Spain.
- Department of Pediatrics and Neonatology, Quironsalud Madrid University Hospital, Madrid, Spain.
- Neonatology Department, La Paz University Hospital - IdiPaz (Hospital La Paz Institute for Health Research), Madrid, Spain.
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.
- Biomedical Data Science Team, Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
- Emergency department, Sant Joan de Déu Hospital, Institut de Recerca Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
- Neonatology department, Sant Joan de Déu Hospital, Institut de Recerca Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
- Universidade Eduardo Mondlane, Faculdade de Medicina, Maputo, Mozambique.
- Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique.
- Maputo Central Hospital, Maputo, Mozambique.
- University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA.
- ISGlobal, Barcelona, Spain.
- Centre national de référence en néonatologie et nutrition - Hȏpital d'enfants-Centre Hospitalier Universitaire Ibn Sina, Rabat, Maroc.
- Équipe de recherche en santé et nutrition du couple mère-enfant, Faculté de Médecine et Pharmacie, Université Mohammed V, Rabat, Maroc.
- Instituto de Tecnologías Físicas y de la Información (CSIC), Madrid, Spain.
- Pediatrics and Infectious Diseases Department, La Paz University Hospital, Fundación IdiPaz, Madrid, Spain.
- Biomedical Research Network Centre for Infectious Diseases (CIBERINFEC), Carlos III Health Institute, Madrid, Spain.
- Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain.
- Universidad Autonoma de Madrid, Madrid, Spain.
- Biomedical Research Foundation, La Paz University Hospital-IDIPAZ, Madrid, Spain.
- ICREA, Pg. Lluís Companys 23, Barcelona, Spain.
- Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Barcelona, Spain.
Abstract
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. 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<sup>3</sup> threshold. The algorithm was applied to 3782 images from 76 patients. It correctly classified 17/18 CSFs with <math xmlns="http://www.w3.org/1998/Math/MathML"><mo>≥</mo></math> 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<sup>3</sup>. This non-invasive device could be an accurate tool for screening meningitis in neonates and young infants, modulating LP indications. 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).