Abstract
BackgroundThe early recognition of meningococcal disease in children is vital. During the prodrome however, meningococcal infection presents similarly to many self-limiting viral infections. This mandates a cautious approach with many children receiving unnecessary broad-spectrum parenteral antibiotics. Advances in nucleic acid amplification techniques mean that it is now possible to test for Neisseria meningitidis DNA using Loop-mediated-isothermal AMPlification (LAMP). This technique is quicker than traditional PCR techniques and can be performed using simple equipment.MethodsPrior to performing this systematic review, a protocol was developed adhering to PRISMA P standards and underwent full external peer review. This systematic review was registered with PROSPERO (CRD42017078026). The index test assessed was LAMP for Neisseria meningitidis and the reference standard was culture or qPCR of a sterile site detecting Neisseria meningitidis.ResultsWe identified 95 records in total: 94 records from the electronic databases and 1 additional study from the grey literature. After removal of duplicates, 36 studies were screened, and 31 studies excluded based on the title/abstract. Five full text studies underwent full text review and three studies, including 2243 tests on 1989 patients aged between 7 days and 18 years were included in the final systematic review. In all studies the LAMP assay and qPCR primers were directed against the ctrA region of the Neisseria meningitidis bacteria. The diagnostic accuracy of LAMP testing for invasive meningococcal disease was reported as high (sensitivity 0.84–1.0 and specificity 0.94–1.0) in all studies irrespective of the sample tested (CSF, Blood, Swab).ConclusionsWe included three studies with 2243 tests on 1989 patients using CSF, blood samples or naso/oropharyngeal swabs. The studies were all of a high quality and deemed at low risk of bias. Results show that LAMP testing on blood and CSF was highly accurate when compared to qPCR/culture.LAMP testing for Neisseria meningitidis is fast and highly accurate and therefore has the potential to be used to rapidly rule in/out meningococcal disease in children. Given the life-threatening nature of meningococcal infection further research is required to demonstrate the safety and efficacy of using LAMP testing for Neisseria meningitidis as a rule in/out test.Trial registrationThis systematic review was registered prospectively with PROSPERO on the 29/11/2017 (CRD42017078026).
Highlights
The early recognition of meningococcal disease in children is vital
In all studies the Loop-mediatedisothermal AMPlification (LAMP) assay and qPCR primers were directed against the ctrA region of the Neisseria meningitidis bacteria
Spiked specimens involve the adding of Neisseria meningitidis Deoxyribonucleic acid (DNA) to human specimens as opposed to detecting wild type Neisseria meningitidis in disease
Summary
Meningococcal infection presents to many self-limiting viral infections This mandates a cautious approach with many children receiving unnecessary broad-spectrum parenteral antibiotics. The challenge is that during the prodrome invasive MD is indistinguishable from many self-limiting viral infections [4,5,6] This mandates a cautious approach to the management of these children with many receiving parenteral antibiotics pending culture results [7]. Attention has moved towards faster and easier molecular testing to allow for earlier diagnosis This has several potential benefits (i) rapid diagnosis of invasive MD at presentation could help to tailor initial treatment (ii) rapid exclusion of invasive MD could shorten the course of parental antibiotics, facilitate earlier discharge or appropriately direct the clinician’s attention towards other infectious diseases
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