Simultaneous detection of gastrointestinal pathogens with a multiplex Luminex-based molecular assay in stool samples from diarrhoeic patients

Mengelle, Catherine; Mansuy, Jean‐Michel; Prère, Marie-Françoise; Grouteau, E.; Claudet, I.; Kamar, Nassim; Huynh, Agnes; Plat, Geneviève; Bénard, Mélinda; Marty, N.; Valentin, Alexis; Berry, Antoine; Izopet, Jacques

doi:10.1111/1469-0691.12255

Cited by 117 publications

(97 citation statements)

References 27 publications

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“…Ten studies [20][21][22][23][24][25][26][27]29,30 reported results of association between the comparator and the GPP test in sufficient detail by pathogen to allow the construction of 2 × 2 tables by pathogen. These studies are further characterised in Table 7 and contributed data to the meta-analysis in Pathogen-level positive and negative agreement.…”

Section: Discussionmentioning

confidence: 99%

“…Only one study 11 differentiated between hospital-based samples (from children admitted with suspected viral gastroenteritis and children presenting to the emergency room) and community-based samples [adult and child travellers whose samples were submitted by general practitioners (GPs)]; the study population consisted of children and travellers only. Seven studies 19,22,26,27,29,35,39 reported the setting sufficiently to allow judgement on the origin of the infection (hospital vs. community). The majority of studies 11,12,20,21,[23][24][25]28,[30][31][32][33][34][36][37][38] reported recruitment of hospitalised patients, for which a mixed population should be assumed (in terms of origin of infection) as it is unclear at what point in time during hospitalisation each infection occurred.…”

Section: Participantsmentioning

confidence: 99%

“…Only one study was identified as a community study, set in Côte d'Ivoire. 19 Subgroups of interest were reported in 10 studies 11,19,20,22,25,26,29,35,36,39 and, of these, one considered travellers only 39 and two considered immunocompromised patients only. 22,26 Children aged < 5 years were not considered separately in any study, but the proportion of children aged < 5 years was reported in six studies 11,19,20,25,35,36 and ranged from 2% to 40% of the total study population.…”

Section: Participantsmentioning

confidence: 99%

“…However, one study reported study-level results for hospital-and community-acquired infections. 27 Country of study Eleven studies 11,22,[27][28][29][30]32,35,[37][38][39] included participants from European countries, including three studies from the UK. 27,30,32 One study was multinational, covering North America and Europe, 21 eight studies were from North America, 12,20,25,26,31,33,34,36 two were from Asia 23,24 and one was from Africa.…”

Section: Participantsmentioning

confidence: 99%

“…According to our definition of the PHE algorithm (see Definitions for the review), only six studies 12,21,26,27,29,36 can be classed as having used a comparator sufficiently similar to the routine screening pathway recommended by PHE in terms of pathogens included (at least 11) and methods used. None of the studies tested patients or samples with all conventional tests.…”

Section: Comparatormentioning

confidence: 99%

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Multiplex tests to identify gastrointestinal bacteria, viruses and parasites in people with suspected infectious gastroenteritis: a systematic review and economic analysis

Freeman

Mistry

Tsertsvadze

et al. 2017

Health Technol Assess

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Background Gastroenteritis is a common, transient disorder usually caused by infection and characterised by the acute onset of diarrhoea. Multiplex gastrointestinal pathogen panel (GPP) tests simultaneously identify common bacterial, viral and parasitic pathogens using molecular testing. By providing test results more rapidly than conventional testing methods, GPP tests might positively influence the treatment and management of patients presenting in hospital or in the community. Objective To systematically review the evidence for GPP tests [xTAG® (Luminex, Toronto, ON, Canada), FilmArray (BioFire Diagnostics, Salt Lake City, UT, USA) and Faecal Pathogens B (AusDiagnostics, Beaconsfield, NSW, Australia)] and to develop a de novo economic model to compare the cost-effectiveness of GPP tests with conventional testing in England and Wales. Data sources Multiple electronic databases including MEDLINE, EMBASE, Web of Science and the Cochrane Database were searched from inception to January 2016 (with supplementary searches of other online resources). Review methods Eligible studies included patients with acute diarrhoea; comparing GPP tests with standard microbiology techniques; and patient, management, test accuracy or cost-effectiveness outcomes. Quality assessment of eligible studies used tailored Quality Assessment of Diagnostic Accuracy Studies-2, Consolidated Health Economic Evaluation Reporting Standards and Philips checklists. The meta-analysis included positive and negative agreement estimated for each pathogen. A de novo decision tree model compared patients managed with GPP testing or comparable coverage with patients managed using conventional tests, within the Public Health England pathway. Economic models included hospital and community management of patients with suspected gastroenteritis. The model estimated costs (in 2014/15 prices) and quality-adjusted life-year losses from a NHS and Personal Social Services perspective. Results Twenty-three studies informed the review of clinical evidence (17 xTAG, four FilmArray, two xTAG and FilmArray, 0 Faecal Pathogens B). No study provided an adequate reference standard with which to compare the test accuracy of GPP with conventional tests. A meta-analysis (of 10 studies) found considerable heterogeneity; however, GPP testing produces a greater number of pathogen-positive findings than conventional testing. It is unclear whether or not these additional ‘positives’ are clinically important. The review identified no robust evidence to inform consequent clinical management of patients. There is considerable uncertainty about the cost-effectiveness of GPP panels used to test for suspected infectious gastroenteritis in hospital and community settings. Uncertainties in the model include length of stay, assumptions about false-positive findings and the costs of tests. Although there is potential for cost-effectiveness in both settings, key modelling assumptions need to be verified and model findings remain tentative. Limitations No test–treat trials were retrieved. The economic model reflects one pattern of care, which will vary across the NHS. Conclusions The systematic review and cost-effectiveness model identify uncertainties about the adoption of GPP tests within the NHS. GPP testing will generally correctly identify pathogens identified by conventional testing; however, these tests also generate considerable additional positive results of uncertain clinical importance. Future work An independent reference standard may not exist to evaluate alternative approaches to testing. A test–treat trial might ascertain whether or not additional GPP ‘positives’ are clinically important or result in overdiagnoses, whether or not earlier diagnosis leads to earlier discharge in patients and what the health consequences of earlier intervention are. Future work might also consider the public health impact of different testing treatments, as test results form the basis for public health surveillance. Study registration This study is registered as PROSPERO CRD2016033320. Funding The National Institute for Health Research Health Technology Assessment programme.

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Section: Discussionmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Comparatormentioning

confidence: 99%

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Multiplex tests to identify gastrointestinal bacteria, viruses and parasites in people with suspected infectious gastroenteritis: a systematic review and economic analysis

Freeman

Mistry

Tsertsvadze

et al. 2017

Health Technol Assess

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Molecular Microbiology

Potula

Tang

2016

Manual of Commercial Methods in Clinical Microbiology

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N 2 -fixation by Rhizobium-legume symbionts is of major ecological and agricultural importance, responsible for producing a substantial fraction of the biosphere's nitrogen. On the basis of 15 N-labelling studies, it had been generally accepted that ammonium is the sole secretion product of N 2 -fixation by the bacteroid and that the plant is responsible for assimilating it into amino acids. However, this paradigm has been challenged in a recent 15 N-labelling study showing that soybean bacteroids only secrete alanine. Hitherto, nitrogen secretion has only been assessed from in vitro 15 N-labelling studies of isolated bacteroids. We show that both ammonium and alanine are secreted by pea bacteroids. The in vitro partitioning between them will depend on whether the system is open or closed, as well as the ammonium concentration and bacteroid density. To overcome these limitations we identified and mutated the gene for alanine dehydrogenase (aldA) and demonstrate that AldA is the primary route for alanine synthesis in isolated bacteroids. Bacteroids of the aldA mutant fix nitrogen but only secrete ammonium at a significant rate, resulting in lower total nitrogen secretion. Peas inoculated with the aldA mutant are green and healthy, demonstrating that ammonium secretion by bacteroids can provide sufficient nitrogen for plant growth. However, plants inoculated with the mutant are reduced in biomass compared with those inoculated with the wild type. The labelling and plant growth studies suggest that alanine synthesis and secretion contributes to the efficiency of N 2fixation and therefore biomass accumulation.

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