Latent TB Infection among US non-institutionalized adults (aged ≥20 years) and children (aged 3–19 years) by sociodemographic correlates and smoking status, 1999–2000.

<p>Latent TB Infection among US non-institutionalized adults (aged ≥20 years) and children (aged 3–19 years) by sociodemographic correlates and smoking status, 1999–2000.</p

Bivariate logistic regression of smoking status and other sociodemographic correlates, and LTBI, United States, 1999–2000.

<p>Bivariate logistic regression of smoking status and other sociodemographic correlates, and LTBI, United States, 1999–2000.</p

Determination of smoking status among those with complete tuberculin skin test (TST) results.

<p>∧Ages 3-11 did not receive smoking behavior questions</p

Estimated US prevalence of LTBI according to smoking characteristics by age and birthplace, 1999–2000.

<p>Estimated US prevalence of LTBI according to smoking characteristics by age and birthplace, 1999–2000.</p

Details of Studies Included in Review and Source of <i>Mycobactrium tuberculosis</i> Isolates.

<p> <b>CDC = Center for Disease Control and Prevention, Atlanta.</b></p

Heatmap of Reviewed Studies that Evaluated <i>rrs</i> Gene Mutations in <i>Mycobacterium tuberculosis</i> isolates.

<p>Graphic shows the region of the <i>rrs</i> gene studied, the number of isolates tested in each study and the locations of the mutations found. The X-axis (nucleotide position) has a 25 base pair resolution. The numbers of isolates varies from 314 (black) to 10 (lightest grey). Red indicates that a mutation has been found in that 25 base pair region.</p

Evaluation of Genetic Mutations Associated with <em>Mycobacterium tuberculosis</em> Resistance to Amikacin, Kanamycin and Capreomycin: A Systematic Review

<div><h3>Background</h3><p>Rapid molecular diagnostics for detecting multidrug-resistant and extensively drug-resistant tuberculosis (M/XDR-TB) primarily identify mutations in <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) genes associated with drug resistance. Their accuracy, however, is dependent largely on the strength of the association between a specific mutation and the phenotypic resistance of the isolate with that mutation, which is not always 100%. While this relationship is well established and reliable for first-line anti-TB drugs, rifampin and isoniazid, it is less well-studied and understood for second-line, injectable drugs, amikacin (AMK), kanamycin (KAN) and capreomycin (CAP).</p> <h3>Methodology/Principal Findings</h3><p>We conducted a systematic review of all published studies evaluating <em>Mtb</em> mutations associated with resistance to AMK, KAN, CAP in order to characterize the diversity and frequency of mutations as well as describe the strength of the association between specific mutations and phenotypic resistance in global populations. Our objective was to determine the potential utility and reliability of these mutations as diagnostic markers for detecting AMK, KAN and CAP resistance. Mutation data was reviewed for 1,585 unique clinical isolates from four continents and over 18 countries. Mutations in the <em>rrs</em>, <em>tlyA</em>, <em>eis</em> promoter and <em>gidB</em> genes were associated with AMK, KAN and/or CAP resistance.</p> <h3>Conclusions/Significance</h3><p>The <em>rrs</em> A1401G mutation was present in the majority of AMK, KAN and CAP resistant <em>Mtb</em> strains reviewed, but was also found in 7% of CAP susceptible strains. The 1401 mutation alone, however, was not found with sufficient frequency to detect more than 70–80% of global <em>Mtb</em> strains resistant to AMK and CAP, and 60% of strains resistant to KAN. Additional mutations in the <em>rrs</em>, <em>eis</em> promoter, <em>tlyA</em> and <em>gidB</em> genes appear to be associated with resistance and could improve sensitivity and specificity of future diagnostics.</p> </div

Cumulative Frequencies of Selected Mutations within the <i>tlyA</i> Gene among <i>Mycobacterium tuberculosis</i> Isolates Resistant or Susceptible to Amikacin (AMK), Kanamycin (KAN) and/or Capreomycin (CAP).

*<p>Represents an amino acid change, as specific nucleotide changes were not provided for this mutation.</p><p>R = Resistant isolates.</p><p>S = Susceptible isolates.</p

Cumulative Frequencies of Multiple Mutations within the <i>rrs</i> Gene among <i>Mycobacterium tuberculosis</i> Isolates Resistant or Susceptible to Amikacin (AMK), Kanamycin (KAN) and/or Capreomycin (CAP).

<p>R = Resistant isolates.</p><p>S = Susceptible isolates.</p

Study Selection Process and Reason for Exclusion of Studies.

<p>Study Selection Process and Reason for Exclusion of Studies.</p