Evaluation of a mNGS Workflow for Infection Diagnosis Using Oxford Nanopore Sequencing.

NCT04864873 | Unknown

• 1 other identifier: MNGS001
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This is a laboratory evaluation of a new testing methodology for microbiological diagnosis, whereby participant samples received as part of routine care will be divided between the standard diagnostic pathway and this new pathway: metagenomic next generation sequencing (mNGS). Results obtained from the mNGS pathway will be compared against the standard diagnostic pathway in terms of sensitivity, specificity, accuracy and clinical impact. The samples will be identified at Wellington Southern Community Laboratories (WSCL), which provides laboratory services for Capital and Coast District Health Board, and forwarded to the Institute of Environmental Science and Research (ESR) to undergo mNGS testing.

Conditions

Bacterial Infections

Keywords

Microbiology; Diagnostics; Metagenomics

Outcome Measures

Primary Outcomes (4)

• Sensitivity of mNGS compared to standard pathway

  Proportion of samples where mNGS detects a pathogenic micro-organism that has been identified by the standard diagnostic pathway.

  Within 1 week of sampling.

• Specificity of mNGS compared to standard pathway

  Proportion of samples where mNGS does not detect a micro-organism where the standard diagnostic pathway has also not detected a micro-organism.

  Within 1 week of sampling.

• Level of agreement between mNGS and standard pathway

  Proportion of samples where the two methods produce the same result.

  Within 1 week of sampling.

• Changes to patient management in response to mNGS result

  The microbiologists involved in the project will assess whether there was a change in treatment or other clinical management in response to the mNGS result. This would include binary outcomes such as a change in antibiotic treatment or whether further investigations (e.g. laboratory or diagnostic radiology) were undertaken.

  Within 1 month of sampling.

Study Arms (2)

Standard diagnostic pathway

ACTIVE COMPARATOR

Part of each patient sample will be tested using current standard microbiological techniques.

Diagnostic Test: Standard microbiological diagnostic pathway

mNGS pathway

EXPERIMENTAL

Part of each sample will be testing using mNGS methodology, which will be compared to the standard diagnostic pathway.

Diagnostic Test: Metagenomic next generation sequencing using Oxford Nanopore

Interventions

Metagenomic next generation sequencing using Oxford Nanopore DIAGNOSTIC_TEST

See previous.

mNGS pathway

Standard microbiological diagnostic pathway DIAGNOSTIC_TEST

See previous.

Standard diagnostic pathway

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All samples received by the WSCL microbiology laboratory for testing for the purposes of diagnosing infection will be eligible.

You may not qualify if:

• Use of residual sample for mNGS testing may leave too little remaining sample and compromise standard diagnostic testing.
• Patients who have requested that their residual samples be returned to them.

Sponsors & Collaborators

• Capital and Coast District Health board: lead
• Wellington Southern Community Laboratories: collaborator
• Institute of Environmental Science and Research: collaborator

Study Sites (1)

Wellington Southern Community Laboratories

Wellington, 6021, New Zealand

RECRUITING

Related Publications (12)

• Ivy MI, Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, Hanssen AD, Abdel MP, Chia N, Yao JZ, Tande AJ, Mandrekar JN, Patel R. Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing. J Clin Microbiol. 2018 Aug 27;56(9):e00402-18. doi: 10.1128/JCM.00402-18. Print 2018 Sep.

  PMID: 29848568 BACKGROUND

• Sanderson ND, Street TL, Foster D, Swann J, Atkins BL, Brent AJ, McNally MA, Oakley S, Taylor A, Peto TEA, Crook DW, Eyre DW. Real-time analysis of nanopore-based metagenomic sequencing from infected orthopaedic devices. BMC Genomics. 2018 Sep 27;19(1):714. doi: 10.1186/s12864-018-5094-y.

  PMID: 30261842 BACKGROUND

• Gu W, Deng X, Lee M, Sucu YD, Arevalo S, Stryke D, Federman S, Gopez A, Reyes K, Zorn K, Sample H, Yu G, Ishpuniani G, Briggs B, Chow ED, Berger A, Wilson MR, Wang C, Hsu E, Miller S, DeRisi JL, Chiu CY. Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids. Nat Med. 2021 Jan;27(1):115-124. doi: 10.1038/s41591-020-1105-z. Epub 2020 Nov 9.

  PMID: 33169017 BACKGROUND

• Street TL, Sanderson ND, Atkins BL, Brent AJ, Cole K, Foster D, McNally MA, Oakley S, Peto L, Taylor A, Peto TEA, Crook DW, Eyre DW. Molecular Diagnosis of Orthopedic-Device-Related Infection Directly from Sonication Fluid by Metagenomic Sequencing. J Clin Microbiol. 2017 Aug;55(8):2334-2347. doi: 10.1128/JCM.00462-17. Epub 2017 May 10.

  PMID: 28490492 BACKGROUND

• Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, Yao JZ, Chia N, Hanssen AD, Abdel MP, Patel R. Identification of Prosthetic Joint Infection Pathogens Using a Shotgun Metagenomics Approach. Clin Infect Dis. 2018 Oct 15;67(9):1333-1338. doi: 10.1093/cid/ciy303.

  PMID: 29648630 BACKGROUND

• Langelier C, Kalantar KL, Moazed F, Wilson MR, Crawford ED, Deiss T, Belzer A, Bolourchi S, Caldera S, Fung M, Jauregui A, Malcolm K, Lyden A, Khan L, Vessel K, Quan J, Zinter M, Chiu CY, Chow ED, Wilson J, Miller S, Matthay MA, Pollard KS, Christenson S, Calfee CS, DeRisi JL. Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12353-E12362. doi: 10.1073/pnas.1809700115. Epub 2018 Nov 27.

  PMID: 30482864 BACKGROUND

• Sanderson ND, Swann J, Barker L, Kavanagh J, Hoosdally S, Crook D; GonFast Investigators Group; Street TL, Eyre DW. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic Nanopore sequencing. Genome Res. 2020 Sep;30(9):1354-1363. doi: 10.1101/gr.262865.120. Epub 2020 Sep 1.

  PMID: 32873606 BACKGROUND

• Rodino KG, Toledano M, Norgan AP, Pritt BS, Binnicker MJ, Yao JD, Aksamit AJ, Patel R. Retrospective Review of Clinical Utility of Shotgun Metagenomic Sequencing Testing of Cerebrospinal Fluid from a U.S. Tertiary Care Medical Center. J Clin Microbiol. 2020 Nov 18;58(12):e01729-20. doi: 10.1128/JCM.01729-20. Print 2020 Nov 18.

  PMID: 32938739 BACKGROUND

• Wu X, Lai T, Jiang J, Ma Y, Tao G, Liu F, Li N. An on-site bacterial detection strategy based on broad-spectrum antibacterial epsilon-polylysine functionalized magnetic nanoparticles combined with a portable fluorometer. Mikrochim Acta. 2019 Jul 10;186(8):526. doi: 10.1007/s00604-019-3632-1.

  PMID: 31292779 BACKGROUND

• Hasan MR, Rawat A, Tang P, Jithesh PV, Thomas E, Tan R, Tilley P. Depletion of Human DNA in Spiked Clinical Specimens for Improvement of Sensitivity of Pathogen Detection by Next-Generation Sequencing. J Clin Microbiol. 2016 Apr;54(4):919-27. doi: 10.1128/JCM.03050-15. Epub 2016 Jan 13.

  PMID: 26763966 BACKGROUND

• Charalampous T, Kay GL, Richardson H, Aydin A, Baldan R, Jeanes C, Rae D, Grundy S, Turner DJ, Wain J, Leggett RM, Livermore DM, O'Grady J. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol. 2019 Jul;37(7):783-792. doi: 10.1038/s41587-019-0156-5. Epub 2019 Jun 24.

  PMID: 31235920 BACKGROUND

• Ji XC, Zhou LF, Li CY, Shi YJ, Wu ML, Zhang Y, Fei XF, Zhao G. Reduction of Human DNA Contamination in Clinical Cerebrospinal Fluid Specimens Improves the Sensitivity of Metagenomic Next-Generation Sequencing. J Mol Neurosci. 2020 May;70(5):659-666. doi: 10.1007/s12031-019-01472-z. Epub 2020 Jan 31.

  PMID: 32002752 BACKGROUND

MeSH Terms

Conditions

Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• Maxim G Bloomfield, MBChB

  Wellington Southern Community Laboratories, Capital and Coast District Health Board

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maxim G Bloomfield, MBChB

CONTACT

+64272089584; maxim.bloomfield@ccdhb.org.nz

Matt Storey

CONTACT

+64210500116; matt.storey@esr.cri.nz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Each patient sample will be divided between standard diagnostic pathways and the mNGS pathway, so each patient will have testing provided by both techniques for direct comparison.

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 29, 2021
• Study Start: May 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)