scholarly journals Metagenomic sequencing as a pathogen-agnostic clinical diagnostic tool for infectious diseases: a systematic review and meta-analysis of diagnostic test accuracy studies

Author(s):  
Kumeren N. Govender ◽  
Teresa L. Street ◽  
Nicholas D. Sanderson ◽  
David W. Eyre

Background: Metagenomic sequencing is frequently claimed to have the potential to revolutionise microbiology through rapid species identification and antimicrobial resistance (AMR) prediction. We assess progress towards this. Methods: We perform a systematic review and meta-analysis of all published literature on culture-independent metagenomic sequencing for pathogen-agnostic infectious disease diagnostics to August 12, 2020. Methodologic bias and applicability were assessed using QUADAS-2. (PROSPERO CRD42020163777) Results: A total of 2023 clinical samples from 13/21 eligible diagnostic test accuracy studies were included in the meta-analysis. Reference standards were culture, molecular testing, clinical decision or a composite measure. Sensitivity and specificity in the most widely investigated sample types were 90%(78-96%) and 86%(45-98%) for blood, 75%(95%CI, 54-89%) and 96%(72-100%) for CSF, and 84%(79-88%) and 67%(38-87%) for orthopaedic samples respectively. We identified limited use of controls, especially negative controls which were used in only 62%(13/21) studies. AMR prediction and comparison to phenotypic results was undertaken in four studies: categorical agreement was 88%(80%-97%), very major and major error rates were 24%(8-40%) and 5%(0-12%) respectively. Better human DNA depletion methods are required: a median 91%(IQR 82-98%)[range 76-98%] of sequences were classified as human. The median(IQR)[range] time from sample to result was 29(24-94)[4-144] hours. The reported consumables cost per sample ranged from $130-$685. Conclusions: There is scope for improving the quality of reporting in clinical metagenomic studies. Although our results are limited by the heterogeneity displayed, our results reflect a promising outlook for clinical metagenomics. Methodological improvements, and convergence around protocols and best practises may improve performance in future.

2021 ◽  
Vol 58 ◽  
pp. 101461
Author(s):  
Stephany Fulda ◽  
Richard P. Allen ◽  
Christopher J. Earley ◽  
Birgit Högl ◽  
Diego Garcia-Borreguero ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pakpoom Subsoontorn ◽  
Manupat Lohitnavy ◽  
Chuenjid Kongkaew

AbstractMany recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction.


Author(s):  
Eunhye Jeong ◽  
Jinkyung Park ◽  
Juneyoung Lee

Under-recognition of delirium is an international problem. For the early detection of delirium, a feasible and valid screening tool for healthcare professionals is needed. This study aimed to present a scientific reason for using the 4 ‘A’s Test (4AT) through a systematic review and meta-analysis of studies on the diagnostic test accuracy. We systematically searched articles in the EMBASE, MEDLINE, CINAHL, and PsycINFO databases and selected relevant articles on the basis of the predefined inclusion criteria. The quality of the included articles was evaluated using the Quality Assessment of the Diagnostic Accuracy Studies-2 tool. We estimated the pooled values of diagnostic test accuracy by employing the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model in data synthesis. A total of 3729 patients of 13 studies were included in the analysis. The pooled estimates of sensitivity and specificity of the 4AT were 81.5% (95% confidence interval: 70.7%, 89.0%) and 87.5% (79.5%, 92.7%), respectively. Given the 4AT’s evidence of accuracy and practicality, we suggest healthcare professionals to utilize this tool for routine screening of delirium. However, for detecting delirium in the dementia population, further work is required to evaluate the 4AT with other cut-off points or scoring methods in order for it to be more sensitive and specific.


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