Developing customized stepwise MIRU-VNTR typing for tuberculosis surveillance in Georgia

• Type of Material: Article
• Authors: Nino Maghradze, Swiss Tropical and Public Health Institute; Levan Jugheli, Swiss Tropical and Public Health Institute; Sonia Borrell, Swiss Tropical and Public Health Institute; Nestani Tukvadze, Swiss Tropical and Public Health Institute; Russell Kempker, Emory University; Henry Blumberg, Emory University; Sebastien Gagneux, Swiss Tropical and Public Health Institute
• Language: English
• Date: 2022-03-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: "This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose."
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0264472
• Title of Journal or Parent Work: PLOS ONE
• Volume: 17
• Issue: 3
• Start Page: e0264472
• End Page: e0264472
• Grant/Funding Information: This work was supported by the Swiss National Science Foundation (grant numbers CRSII5_177163 and 310030_188888) – Sebastien Gagneux, the European Research Council (ECOEVODRTB_883582) – Sebastien Gagneux, and from the U.S. National Institute of Health (NIH) Fogarty International Center (D43TW007124) - Russell R Kempker, Henry M. Blumberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: DIVERSITY; STRAINS; Multidisciplinary Sciences; Science & Technology - Other Topics; MYCOBACTERIUM-TUBERCULOSIS; Science & Technology

Abstract

Introduction: Mycobacterial Interspersed Repetitive Units-Variable Tandem Repeats (MIRU-VNTR) typing has been widely used for molecular epidemiological studies of tuberculosis (TB). However, genotyping tools for Mycobacterium tuberculosis (Mtb) may be limiting in some settings due to high cost and workload. In this study developed a customized stepwise MIRU-VNTR typing that prioritizes high discriminatory loci and validated this method using penitentiary system cohort in the country of Georgia. Methods: We used a previously generated MIRU-VNTR dataset from recurrent TB cases (32 cases) in Georgia and a new dataset of TB cases from the penitentiary system (102 cases) recruited from 2014 to 2015. A Hunter-Gaston Discriminatory Index (HGDI) was calculated utilizing a 24 standard loci panel, to select high discriminatory power loci, subsequently defined as the customized Georgia-specific set of loci for initial typing. The remaining loci were scored and hierarchically grouped for second and third step typing of the cohort. We then compared the processing time and costs of the customized stepwise method to the standard 24-loci method. Results: For the customized Georgia-specific set that was used for initial typing, 10 loci were selected with a minimum value of 0.32 to the highest HGDI score locus. Customized 10 loci (step 1) typing of 102 Mtb patient isolates revealed 35.7% clustered cases. This proportion was reduced to 19.5% after hierarchical application of 2ndand 3rdstep typing with the corresponding groups of loci. Our customized stepwise MIRU-VNTR genotyping approach reduced the quantity of samples to be typed and therefore overall processing time and costs by 42.6% each. Conclusion: Our study shows that our customized stepwise MIRU-VNTR typing approach is a valid alternative of standard MIRI-VNTR typing panels for molecular epidemiological investigation in Georgia that saves time, workload and costs. Similar approaches could be developed for other settings.