Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study

Abstract

Laboratory diagnosis and clinical management of inpatients with diarrhoea is complex and time consuming. Tests are often requested sequentially and undertaken in different laboratories. This causes prolonged unnecessary presumptive isolation of patients, because most cases are non-infectious. A molecular multiplex test (Luminex(®) Gastrointestinal Pathogen Panel (GPP)) was compared with conventional testing over 8 months to determine diagnostic accuracy, turnaround times, laboratory costs, use of isolation facilities and user acceptability. A total of 262 (12%) patients had a pathogen detected by conventional methods compared with 483 (22.1%) by GPP. Most additional cases were detected in patients developing symptoms in the first 4 days of admission. Additional cases were detected because of presumed improved diagnostic sensitivity but also because clinicians had not requested the correct pathogen. Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite investigation (66.5 h) but slower than conventional testing for Clostridium difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting by clinicians and a consolidated laboratory workflow, reducing the overall number of specimens received by the laboratory. A total of 154 isolation days were saved at an estimated cost of £30 800. Consumables and labour were estimated at £150 641 compared with £63 431 for conventional testing. Multiplex molecular testing using a panel of targets allowed enhanced detection and a consolidated laboratory workflow. This is likely to be of greater benefit to cases that present within the first 4 days of hospital admission.

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

“…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.…”

“…Studies retrospectively included samples with confirmed gastroenteritis and negative controls 30 or prospectively included samples from patients with suspected gastroenteritis. [20][21][22][23][24][25][26][27]29 Comparator and GPP tests were both undertaken at the study site(s) in seven studies, [22][23][24][25][26][27]29 whereas one study sent the samples to reference laboratories for conventional testing, 30 one study sent the samples to Luminex for GPP testing 21 and one study sent the samples to BioFire for comparator testing. 20 Verification was undertaken on all discrepant samples by four studies, 20 29 The remaining three studies, 24,26,27 which did not undertake verification, assumed either that the comparator methods are the reference standard to calculate sensitivity and specificity 24,26 or assumed that the GPP assay is correct and did not calculate sensitivity and specificity because of the lack of a resolving assay.…”

“…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.…”

“…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. 19 Therefore, the applicability of the study population in terms of prevalence of pathogens is questionable in 3 out of the 23 studies (see Quality considerations of included studies).…”

“…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.…”