Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission
Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable an...
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Frontiers Media S.A.
2022-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2021.790544/full |
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author | Kristin N. Nelson Sarah Talarico Shameer Poonja Clinton J. McDaniel Martin Cilnis Alicia H. Chang Kala Raz Wendy S. Noboa Lauren Cowan Tambi Shaw James Posey Benjamin J. Silk |
author_facet | Kristin N. Nelson Sarah Talarico Shameer Poonja Clinton J. McDaniel Martin Cilnis Alicia H. Chang Kala Raz Wendy S. Noboa Lauren Cowan Tambi Shaw James Posey Benjamin J. Silk |
author_sort | Kristin N. Nelson |
collection | DOAJ |
description | Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission. |
first_indexed | 2024-04-11T17:15:54Z |
format | Article |
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institution | Directory Open Access Journal |
issn | 2296-2565 |
language | English |
last_indexed | 2024-04-11T17:15:54Z |
publishDate | 2022-01-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Public Health |
spelling | doaj.art-7bd190e79b4e444b840bc82f92a3a4dd2022-12-22T04:12:41ZengFrontiers Media S.A.Frontiers in Public Health2296-25652022-01-01910.3389/fpubh.2021.790544790544Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis TransmissionKristin N. Nelson0Sarah Talarico1Shameer Poonja2Clinton J. McDaniel3Martin Cilnis4Alicia H. Chang5Kala Raz6Wendy S. Noboa7Lauren Cowan8Tambi Shaw9James Posey10Benjamin J. Silk11Rollins School of Public Health, Emory University, Atlanta, GA, United StatesDivision of Tuberculosis Elimination, National Center for HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome), Viral Hepatitis, STD (Sexually Transmitted Diseases), and Tuberculosis (TB) Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United StatesLos Angeles County Department of Public Health, Los Angeles, CA, United StatesDivision of Tuberculosis Elimination, National Center for HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome), Viral Hepatitis, STD (Sexually Transmitted Diseases), and Tuberculosis (TB) Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United StatesTB Control Branch, California Department of Public Health, Richmond, CA, United StatesLos Angeles County Department of Public Health, Los Angeles, CA, United StatesDivision of Tuberculosis Elimination, National Center for HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome), Viral Hepatitis, STD (Sexually Transmitted Diseases), and Tuberculosis (TB) Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United StatesLos Angeles County Department of Public Health, Los Angeles, CA, United StatesDivision of Tuberculosis Elimination, National Center for HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome), Viral Hepatitis, STD (Sexually Transmitted Diseases), and Tuberculosis (TB) Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United StatesTB Control Branch, California Department of Public Health, Richmond, CA, United StatesDivision of Tuberculosis Elimination, National Center for HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome), Viral Hepatitis, STD (Sexually Transmitted Diseases), and Tuberculosis (TB) Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United StatesDivision of Tuberculosis Elimination, National Center for HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome), Viral Hepatitis, STD (Sexually Transmitted Diseases), and Tuberculosis (TB) Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United StatesTuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.https://www.frontiersin.org/articles/10.3389/fpubh.2021.790544/fulltuberculosis—epidemiologyprevention and controlgenomic sequencingtuberculosis transmissionpublic health practice |
spellingShingle | Kristin N. Nelson Sarah Talarico Shameer Poonja Clinton J. McDaniel Martin Cilnis Alicia H. Chang Kala Raz Wendy S. Noboa Lauren Cowan Tambi Shaw James Posey Benjamin J. Silk Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission Frontiers in Public Health tuberculosis—epidemiology prevention and control genomic sequencing tuberculosis transmission public health practice |
title | Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission |
title_full | Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission |
title_fullStr | Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission |
title_full_unstemmed | Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission |
title_short | Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission |
title_sort | mutation of mycobacterium tuberculosis and implications for using whole genome sequencing for investigating recent tuberculosis transmission |
topic | tuberculosis—epidemiology prevention and control genomic sequencing tuberculosis transmission public health practice |
url | https://www.frontiersin.org/articles/10.3389/fpubh.2021.790544/full |
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