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Rapid Accurate Identification of Tuberculous Meningitis Among South African Children Using a Novel Clinical Decision Tool

Goenka, Anu, MRCPCH*†‡; Jeena, Prakash, M., PhD§; Mlisana, Koleka, PhD¶‖; Solomon, Tom, PhD**††; Spicer, Kevin, PhD‡§; Stephenson, Rebecca, MRCPCH; Verma, Arpana, PhD†‡‡; Dhada, Barnesh, FCPaed (SA)‡§; Griffiths, Michael, J., PhD**§§

The Pediatric Infectious Disease Journal: March 2018 - Volume 37 - Issue 3 - p 229–234
doi: 10.1097/INF.0000000000001726
Original Studies

Background: Early diagnosis of tuberculous meningitis (TBM) is crucial to achieve optimum outcomes. There is no effective rapid diagnostic test for use in children. We aimed to develop a clinical decision tool to facilitate the early diagnosis of childhood TBM.

Methods: Retrospective case–control study was performed across 7 hospitals in KwaZulu-Natal, South Africa (2010–2014). We identified the variables most predictive of microbiologically confirmed TBM in children (3 months to 15 years) by univariate analysis. These variables were modelled into a clinical decision tool and performance tested on an independent sample group.

Results: Of 865 children with suspected TBM, 3% (25) were identified with microbiologically confirmed TBM. Clinical information was retrieved for 22 microbiologically confirmed cases of TBM and compared with 66 controls matched for age, ethnicity, sex and geographical origin. The 9 most predictive variables among the confirmed cases were used to develop a clinical decision tool (CHILD TB LP): altered Consciousness; caregiver HIV infected; Illness length >7 days; Lethargy; focal neurologic Deficit; failure to Thrive; Blood/serum sodium <132 mmol/L; CSF >10 Lymphocytes ×106/L; CSF Protein >0.65 g/L. This tool successfully classified an independent sample of 7 cases and 21 controls with a sensitivity of 100% and specificity of 90%.

Conclusions: The CHILD TB LP decision tool accurately classified microbiologically confirmed TBM. We propose that CHILD TB LP is prospectively evaluated as a novel rapid diagnostic tool for use in the initial evaluation of children with suspected neurologic infection presenting to hospitals in similar settings.

From the *Manchester Collaborative Centre for Inflammation Research, Manchester Academic Health Sciences Centre, and ‡‡Centre for Epidemiology, Institute of Population Health, University of Manchester, United Kingdom; Department of Paediatrics and Child Health, Pietermaritzburg Metropolitan Hospitals Complex, Pietermaritzburg, South Africa; §Department of Paediatrics and Child Health, and School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, and Department of Microbiology, National Health Laboratory Service, Durban, South Africa; and **Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection and Global Health, University of Liverpool, ††Walton Centre NHS Foundation Trust, and §§Department of Neurology, Alder Hey Children’s NHS Trust, Liverpool, United Kingdom.

Accepted for publication July 24, 2017.

A. G. was supported by a Royal College of Physicians Thomas Watts Eden Fellowship. This study was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE) and Liverpool School of Tropical Medicine (LSTM). The views expressed are those of the author(s) and not necessarily those of the NHS (National Health Service), the NIHR and the Department of Health or Public Health England.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Anu Goenka, MRCPCH, Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT, United Kingdom. E-mail: anu.goenka@manchester.ac.uk.

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