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Loop-mediated isothermal amplification for the early diagnosis of invasive meningococcal disease in children
  1. Thomas Waterfield1,2,
  2. Mark D Lyttle3,4,
  3. James McKenna5,
  4. Julie-Ann Maney6,
  5. Damian Roland7,8,
  6. Michael Corr9,
  7. Kerry Woolfall10,
  8. Bethany Patenall11,
  9. Michael Shields1,12,
  10. Derek Fairley12
  11. on behalf of Paediatric Emergency Research in the UK and Ireland (PERUKI)
  1. 1Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
  2. 2Emergency Department, Royal Belfast Children's Hospital, Belfast, UK
  3. 3Emergency Department, Bristol Royal Hospital for Children, Bristol, UK
  4. 4Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK
  5. 5Department of Microbiology, Belfast Health and Social Care Trust, Belfast, UK
  6. 6Emergency Department, Royal Belfast Hospital for Sick Children, Belfast, UK
  7. 7SAPPHIRE Group, Health Sciences, University of Leicester, Leicester, UK
  8. 8Paediatric Emergency Medicine Leicester Academic (PEMLA) Group, Leicester Hospitals, Leicester, UK
  9. 9Belfast Health and Social Care Trust, Belfast, UK
  10. 10Institute of Psychology, University of Liverpool, Liverpool, UK
  11. 11Department of Chemistry, University of Bath, Bath, Somerset, UK
  12. 12The Royal Belfast Hospital for Sick Children, Belfast, UK
  1. Correspondence to Dr Thomas Waterfield, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK; thomas.waterfield{at}googlemail.com

Abstract

Background Rapid molecular diagnostic testing has the potential to improve the early recognition of meningococcal disease (MD). The aim of this study was to report on the diagnostic test accuracy of point-of-care loop-mediated isothermal amplification (LAMP) in the diagnosis of MD.

Design Data were collected prospectively from three UK emergency departments (ED) between November 2017 and June 2019. Consecutive children under 18 years of age attending the ED with features of MD were eligible for inclusion. The meningococcal LAMP test (index test) was performed on a dry swab of the child’s oropharynx. Reference standard testing was the confirmation of invasive MD defined as positive N. meningitidis culture or PCR result from a sterile body site (blood or cerebrospinal fluid).

Results There were 260 children included in the final analysis. The median age was 2 years 11 months and 169 (65%) children were aged 5 years or younger. The LAMP test was negative in 246 children and positive in 14 children. Of the 14 children with positive LAMP tests, there were five cases of invasive MD. Of the 246 children with negative LAMP tests, there were no cases of invasive MD. The sensitivity of LAMP testing was 1.00 and the specificity was 0.97. The negative and positive predictive values were 1.00 and 0.36, respectively. The positive likelihood ratio was 28.3.

Discussion Non-invasive LAMP testing using oropharyngeal swabs provided an accurate fast and minimally invasive mechanism for predicting invasive MD in this study.

Trial registration number NCT03378258.

  • general paediatrics
  • infectious diseases
  • accident & emergency
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Footnotes

  • Twitter @mdlyttle, @julieannmaney, @damian_roland

  • Contributors TW, MDL, DR, J-AM, DF, JM and MS conceived and designed the study. TW co-ordinated the running of the study including data management and site training. MC and BP were involved with the conduct of the study including data collection. KW provided study design expertise and designed the approach to consent.

  • Funding This study was primarily funded by the Public Health Agency of Northern Ireland (EAT/5313/16). The Royal College of Emergency Medicine provided some additional funding. The funder had no involvement in the design or conduct of the study.

  • Competing interests JM Holds share options in HiberGene Diagnostics Ltd.

  • Patient consent for publication Not required.

  • Ethics approval The Northern Ireland Research Ethics Committee (REC Reference—17/NI/0169) and the Belfast Health & Social Care Trust Research Governance (Reference 16 201MS-SW) approved the protocol.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. All of the individual participant data collected during this study will be available (including data dictionaries) on the Queen’s University Belfast data repository. The full study protocol is available as an open access publication.

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