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      A systematic review of the diagnostic accuracy of Loop-mediated-isothermal AMPlification (LAMP) in the diagnosis of invasive meningococcal disease in children

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          Abstract

          Background

          The 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.

          Methods

          Prior 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.

          Results

          We 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).

          Conclusions

          We 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 ha s 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 registration

          This systematic review was registered prospectively with PROSPERO on the 29/11/2017 (CRD42017078026).

          Electronic supplementary material

          The online version of this article (10.1186/s12887-019-1403-0) contains supplementary material, which is available to authorized users.

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          Most cited references19

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          The nuts and bolts of PROSPERO: an international prospective register of systematic reviews

          Background Following publication of the PRISMA statement, the UK Centre for Reviews and Dissemination (CRD) at the University of York in England began to develop an international prospective register of systematic reviews with health-related outcomes. The objectives were to reduce unplanned duplication of reviews and provide transparency in the review process, with the aim of minimizing reporting bias. Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality. This article describes the development of the register, now called PROSPERO, and the process of registration. Results PROSPERO offers free registration and free public access to a unique prospective register of systematic reviews across all areas of health from all around the world. The dedicated web-based interface is electronically searchable and available to all prospective registrants. At the moment, inclusion in PROSPERO is restricted to systematic reviews of the effects of interventions and strategies to prevent, diagnose, treat, and monitor health conditions, for which there is a health-related outcome. Ideally, registration should take place before the researchers have started formal screening against inclusion criteria but reviews are eligible as long as they have not progressed beyond the point of completing data extraction. The required dataset captures the key attributes of review design as well as the administrative details necessary for registration. Submitted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register, rejected, or returned to the applicant for clarification. The public records include an audit trail of major changes to planned methods, details of when the review has been completed, and links to resulting publications when provided by the authors. Conclusions There has been international support and an enthusiastic response to the principle of prospective registration of protocols for systematic reviews and to the development of PROSPERO. In October 2011, PROSPERO contained 200 records of systematic reviews being undertaken in 26 countries around the world on a diverse range of interventions.
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            Meningococcal carriage by age: a systematic review and meta-analysis.

            Neisseria meningitidis is an important cause of meningitis and septicaemia, but most infected individuals experience a period of asymptomatic carriage rather than disease. Previous studies have shown that carriage rates vary by age and setting; however, few have assessed carriage across all ages. We aimed to estimate the age-specific prevalence of meningococcal carriage. We searched Embase, Medline, Web of Science, the Cochrane Library, and grey literature for papers reporting carriage of N meningitidis in defined age groups in European countries or in countries with a similar epidemiological pattern (where disease caused by serogroups B and C predominates). We used mixed-effects logistic regression with a natural cubic spline to model carriage prevalence as a function of age for studies that were cross-sectional or serial cross-sectional. The model assessed population type, type of swab used, when swabs were plated, use of preheated plates, and time period (decade of study) as fixed effects, with country and study as nested random effects (random intercept). Carriage prevalence increased through childhood from 4·5% in infants to a peak of 23·7% in 19-year olds and subsequently decreased in adulthood to 7·8% in 50-year olds. The odds of testing positive for carriage decreased if swabs were not plated immediately after being taken compared with if swabs were plated immediately (odds ratio 0·46, 95% CI 0·31-0·68; p = 0·0001). This study provides estimates of carriage prevalence across all ages, which is important for understanding the epidemiology and transmission dynamics of meningococcal infection. None. Copyright © 2010 Elsevier Ltd. All rights reserved.
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              Meningococcal disease during the Hajj and Umrah mass gatherings.

              The Hajj and Umrah religious mass gatherings hosted by the Kingdom of Saudi Arabia can facilitate the transmission of infectious diseases. The pilgrimages have been associated with a number of local and international outbreaks of meningococcal disease. These include serogroup A disease outbreaks in 1987 and throughout the 1990s and two international serogroup W135 outbreaks in 2000 and 2001. The implementation of strict preventative measures including mandatory quadrivalent meningococcal vaccination and antibiotic chemoprophylaxis for pilgrims from the African meningitis belt has prevented pilgrimage-associated meningococcal outbreaks since 2001. However, the fluid epidemiology of the disease and the possibility of outbreaks caused by serogroups not covered by the vaccine or emerging hyper-virulent strains, mean that the disease remains a serious public health threat during these events. Continuous surveillance of carriage state and the epidemiology of the disease in the Kingdom and globally and the introduction of preventative measures that provide broad and long-lasting immunity and impact carriage are warranted.
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                Author and article information

                Contributors
                02890976378 , twaterfield01@qub.ac.uk
                derek.fairley@belfasttrust.hscni.net
                b.blackwood@qub.ac.uk
                James.McKenna@belfasttrust.hscni.net
                m.shields@qub.ac.uk
                Journal
                BMC Pediatr
                BMC Pediatr
                BMC Pediatrics
                BioMed Central (London )
                1471-2431
                7 February 2019
                7 February 2019
                2019
                : 19
                : 49
                Affiliations
                [1 ]ISNI 0000 0004 0374 7521, GRID grid.4777.3, Centre for Experimental Medicine, , Queen’s University Belfast, Wellcome Wolfson Institute of Experimental Medicine, ; 97 Lisburn Road, Belfast, BT9 7AE UK
                [2 ]ISNI 0000 0000 9565 2378, GRID grid.412915.a, Belfast Health and Social Care Trust, ; Belfast, UK
                Author information
                http://orcid.org/0000-0001-9452-7716
                Article
                1403
                10.1186/s12887-019-1403-0
                6366060
                30732581
                8c48ab66-56d9-4611-a736-f56bcf2c3175
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 June 2018
                : 14 January 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Pediatrics
                meningococcal,meningitis,sepsis,neisseria meningitidis,test accuracy,meta-analysis
                Pediatrics
                meningococcal, meningitis, sepsis, neisseria meningitidis, test accuracy, meta-analysis

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