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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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Public Health
Subjects:
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.
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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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