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RATIONALE: Delays in the diagnosis of tuberculosis (TB) can result in progression to advanced disease. Patients with pulmonary TB and advanced disease are more likely to transmit disease and fail treatment. OBJECTIVES: To examine clinical, epidemiological, and geographic factors associated with advanced pulmonary TB to further understanding of delayed diagnosis and transmission. METHODS: Pulmonary tuberculosis cases in persons older than 15 years of age reported to the U.S. National Tuberculosis Surveillance System with advanced disease (cavitation on chest radiograph and acid-fast bacilli smear-positive sputum result) were compared with those without advanced disease using trend and binomial regression analysis. MEASUREMENTS AND MAIN RESULTS: There were 35,584 cases of advanced pulmonary tuberculosis (APT) and 125,077 cases of non-APT reported from 1993 through 2006. Proportions of pulmonary TB cases with APT increased from 18.5% in 1993 to 26.1% in 2006, and the increase in the proportion of APT was most notable for national TB rates below 6.6 per 100,000. At the county level, the association between APT and low TB incidence has grown incrementally since 2000. The proportion of APT increased greatest among whites (65.4%), the employed (63.3%), and the U.S. born (59.2%). The prevalence of APT was 44% greater among persons with multidrug-resistant TB compared with those without it. CONCLUSIONS: This study highlights the need for TB diagnosis at early stages of the disease to minimize APT and decrease the risk of transmission. Additional efforts should concentrate on reducing time to treatment initiation in low-incidence areas and among groups traditionally seen as being at low risk for TB disease. [ABSTRACT FROM AUTHOR]

Background: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods., Methods: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS., Results: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively., Conclusions: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Culture-based diagnostics are the gold standard for diagnosing pulmonary TB (PTB). We characterized culture practices by comparing cases with documented sputum culture to those without.Using multivariable logistic regression, we examined associations between PTB case characteristics and no documented sputum culture reported to the U.S. National TB Surveillance System during 2011-2021.Among 69,538 PTB cases analyzed, no sputum culture attempt was documented for 5,869 (8%). Non-sputum culture specimens were documented for 54%, 80%, and 89% of cases without documented sputum culture attempts among persons aged <15 years, 15-64, and 65+ years, respectively; bronchial fluid and lung tissue were common non-sputum specimens among cases in persons >15 years old. Having no documented sputum culture was associated with age <15 years (aOR 23.84, 99% CI 20.09-28.27) or ≥65 years (aOR 1.22, 99% CI 1.07-1.39), culture of a non-sputum specimen (aOR 6.57, 99% CI 5.93-7.28), residence in a long-term care facility (aOR 1.58, 99% CI 1.23-2.01), and receiving TB care outside of a health department (aOR 1.79, 99% CI 1.61-1.98).Inability to obtain sputum from children and higher diagnostic suspicion for disease processes that require tissue-based diagnostics could explain these findings..

Background: In the United States, over 80% of tuberculosis (TB) disease cases are estimated to result from reactivation of latent TB infection (LTBI) acquired more than 2 years previously ("reactivation TB"). We estimated reactivation TB rates for the US population with LTBI, overall, by age, sex, race-ethnicity, and US-born status, and for selected comorbidities (diabetes, end-stage renal disease, and HIV)., Methods: We collated nationally representative data for 2011-2012. Reactivation TB incidence was based on TB cases reported to the National TB Surveillance System that were attributed to LTBI reactivation. Person-years at risk of reactivation TB were calculated using interferon-gamma release assay (IGRA) positivity from the National Health and Nutrition Examination Survey, published values for interferon-gamma release assay sensitivity and specificity, and population estimates from the American Community Survey., Results: For persons aged ≥6 years with LTBI, the overall reactivation rate was estimated as 0.072 (95% uncertainty interval: 0.047, 0.12) per 100 person-years. Estimated reactivation rates declined with age. Compared to the overall population, estimated reactivation rates were higher for persons with diabetes (adjusted rate ratio [aRR] = 1.6 [1.5, 1.7]), end-stage renal disease (aRR = 9.8 [5.4, 19]), and HIV (aRR = 12 [10, 13])., Conclusions: In our study, individuals with LTBI faced small, non-negligible risks of reactivation TB. Risks were elevated for individuals with medical comorbidities that weaken immune function., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: American Indian and Alaska Native (AIAN) populations are frequently associated with the highest rates of tuberculosis (TB) disease of any racial/ethnic group in the USA. We systematically investigated variation in patterns and potential drivers of TB epidemiology among geographically distinct AIAN subgroups., Methods: Using data reported to the National Tuberculosis Surveillance System during 2010-2020, we applied a geographic method of data disaggregation to compare annual TB incidence and the frequency of TB patient characteristics among AIAN persons in Alaska with AIAN persons in other states. We used US Census data to compare the prevalence of substandard housing conditions in AIAN communities in these two geographic areas., Results: The average annual age-adjusted TB incidence among AIAN persons in Alaska was 21 times higher than among AIAN persons in other states. Compared to AIAN TB patients in other states, AIAN TB patients in Alaska were associated with significantly higher frequencies of multiple epidemiologic TB risk factors (e.g., attribution of TB disease to recent transmission, previous diagnosis of TB disease) and significantly lower frequencies of multiple clinical risk factors for TB disease (e.g., diagnosis with diabetes mellitus, end-stage renal disease). Occupied housing units in AIAN communities in Alaska were associated with significantly higher frequencies of multiple measures of substandard housing conditions compared to AIAN communities in other states., Conclusions: Observed differences in patient characteristics and substandard housing conditions are consistent with contrasting syndromes of TB epidemiology in geographically distinct AIAN subgroups and suggest ways that associated public health interventions could be tailored to improve efficacy., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Reductions in tuberculosis (TB) transmission have been instrumental in lowering TB incidence in the United States. Sustaining and augmenting these reductions are key public health priorities., Methods: We fit mechanistic transmission models to distributions of genotype clusters of TB cases reported to the Centers for Disease Control and Prevention during 2012-2016 in the United States and separately in California, Florida, New York, and Texas. We estimated the mean number of secondary cases generated per infectious case (R0) and individual-level heterogeneity in R0 at state and national levels and assessed how different definitions of clustering affected these estimates., Results: In clusters of genotypically linked TB cases that occurred within a state over a 5-year period (reference scenario), the estimated R0 was 0.29 (95% confidence interval [CI], .28-.31) in the United States. Transmission was highly heterogeneous; 0.24% of simulated cases with individual R0 >10 generated 19% of all recent secondary transmissions. R0 estimate was 0.16 (95% CI, .15-.17) when a cluster was defined as cases occurring within the same county over a 3-year period. Transmission varied across states: estimated R0s were 0.34 (95% CI, .3-.4) in California, 0.28 (95% CI, .24-.36) in Florida, 0.19 (95% CI, .15-.27) in New York, and 0.38 (95% CI, .33-.46) in Texas., Conclusions: TB transmission in the United States is characterized by pronounced heterogeneity at the individual and state levels. Improving detection of transmission clusters through incorporation of whole-genome sequencing and identifying the drivers of this heterogeneity will be essential to reducing TB transmission., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Populations of indigenous persons are frequently associated with pronounced disparities in rates of tuberculosis (TB) disease compared to co-occurring nonindigenous populations., Methods: Using data from the National Tuberculosis Surveillance System on TB cases in U.S.-born patients reported in the United States during 2009-2019, we calculated incidence rate ratios and risk ratios for TB risk factors to compare cases in American Indian or Alaska Native (AIAN) and Native Hawaiian or other Pacific Islander (NHPI) TB patients to cases in White TB patients., Results: Annual TB incidence rates among AIAN and NHPI TB patients were on average ≥10 times higher than among White TB patients. Compared to White TB patients, AIAN and NHPI TB patients were 1.91 (95% confidence interval (CI): 1.35-2.71) and 3.39 (CI: 1.44-5.74) times more likely to have renal disease or failure, 1.33 (CI: 1.16-1.53) and 1.63 (CI: 1.20-2.20) times more likely to have diabetes mellitus, and 0.66 (CI: 0.44-0.99) and 0.19 (CI: 0-0.59) times less likely to be HIV positive, respectively. AIAN TB patients were 1.84 (CI: 1.69-2.00) and 1.48 (CI: 1.27-1.71) times more likely to report using excess alcohol and experiencing homelessness, respectively., Conclusion: TB among U.S. indigenous persons is associated with persistent and concerning health disparities., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018., Methods: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases., Results: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission., Conclusion: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Objectives. To understand the frequency, magnitude, geography, and characteristics of tuberculosis outbreaks in US state prisons. Methods. Using data from the National Tuberculosis Surveillance System, we identified all cases of tuberculosis during 2011 to 2019 that were reported as occurring among individuals incarcerated in a state prison at the time of diagnosis. We used whole-genome sequencing to define 3 or more cases within 2 single nucleotide polymorphisms within 3 years as clustered; we classified clusters with 6 or more cases during a 3-year period as tuberculosis outbreaks. Results. During 2011 to 2019, 566 tuberculosis cases occurred in 41 state prison systems (a median of 3 cases per state). A total of 19 tuberculosis genotype clusters comprising 134 cases were identified in 6 state prison systems; these clusters included a subset of 5 outbreaks in 2 states. Two Alabama outbreaks during 2011 to 2017 totaled 20 cases; 3 Texas outbreaks during 2014 to 2019 totaled 51 cases. Conclusions. Only Alabama and Texas reported outbreaks during the 9-year period; only Texas state prisons had ongoing transmission in 2019. Effective interventions are needed to stop tuberculosis outbreaks in Texas state prisons. ( Am J Public Health . 2022;112(8):1170-1179. https://doi.org/10.2105/AJPH.2022.306864).

Background: Older age is a risk factor for tuberculosis (TB) in low incidence settings. Using data from the US National TB Surveillance System and American Community Survey, we estimated trends and racial/ethnic differences in TB incidence among US-born cohorts aged ≥50 years., Methods: In total, 42 000 TB cases among US-born persons ≥50 years were reported during 2001-2019. We used generalized additive regression models to decompose the effects of birth cohort and age on TB incidence rates, stratified by sex and race/ethnicity. Using genotype-based estimates of recent transmission (available 2011-2019), we implemented additional models to decompose incidence trends by estimated recent versus remote infection., Results: Estimated incidence rates declined with age, for the overall cohort and most sex and race/ethnicity strata. Average annual percentage declines flattened for older individuals, from 8.80% (95% confidence interval [CI] 8.34-9.23) in 51-year-olds to 4.51% (95% CI 3.87-5.14) in 90-year-olds. Controlling for age, incidence rates were lower for more recent birth cohorts, dropping 8.79% (95% CI 6.13-11.26) on average between successive cohort years. Incidence rates were substantially higher for racial/ethnic minorities, and these inequalities persisted across all birth cohorts. Rates from recent infection declined at approximately 10% per year as individuals aged. Rates from remote infection declined more slowly with age, and this annual percentage decline approached zero for the oldest individuals., Conclusions: TB rates were highest for racial/ethnic minorities and for the earliest birth cohorts and declined with age. For the oldest individuals, annual percentage declines were low, and most cases were attributed to remote infection., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Context: Resistance to isoniazid (INH) only (monoresistance), with drug susceptibility to rifampin, pyrazinamide, and ethambutol at diagnosis of tuberculosis (TB) disease, can increase the length of treatment., Objective: To describe US trends in INH monoresistance and associated patient characteristics., Design: We performed trend and cross-sectional analyses of US National Tuberculosis Surveillance System surveillance data. We used Joinpoint regression to analyze annual trends in INH monoresistance and logistic regression to identify patient characteristics associated with INH monoresistance., Participants: Culture-positive cases reported to National Tuberculosis Surveillance System during 1993-2016 with drug susceptibility test results to INH, rifampin, pyrazinamide, and ethambutol., Main Outcome Measures: (1) Trends in INH monoresistance; (2) odds ratios for factors associated with INH monoresistance., Results: Isoniazid monoresistance increased significantly from 4.1% of all TB cases in 1993 to 4.9% in 2016. Among US-born patients, INH monoresistance increased significantly from 2003 onward (annual percentage change = 2.8%; 95% confidence interval: 1.4-4.2). During 2003-2016, US-born persons with INH-monoresistant TB were more likely to be younger than 65 years; to be Asian; to be human immunodeficiency virus-infected; or to be a correctional facility resident at the time of diagnosis. Among non-US-born persons, INH resistance did not change significantly during 1993-2016 (annual percentage change = -0.3%; 95% confidence interval: -0.7 to 0.2) and was associated with being aged 15 to 64 years; being Asian, black, or Hispanic; or having a previous history of TB., Conclusions: INH-monoresistant TB has been stable since 1993 among non-US-born persons; it has increased 2.8% annually among US-born persons during 2003-2016. Reasons for this increase should be further investigated., Competing Interests: The authors have no nongovernmental sources of funding or conflicts of interest to declare for this research., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: To describe diabetes trends among adults with incident tuberculosis (TB) disease and examine diabetes-associated TB characteristics and patient outcomes in the USA., Research Design and Methods: We examined all 71 855 persons aged ≥20 years with incident TB disease reported to the National Tuberculosis Surveillance System during 2010-2017. We performed multivariable logistic regression, comparing characteristics and outcomes among patients with TB reported to have diabetes and those whose diabetes status was unknown., Results: An overall 18% (n=13 281) of the 71 855 adults with incident TB disease were reported as also having diabetes; the annual proportion increased from 15% in 2010 to 22% in 2017. Among patients aged ≥45 years with both TB and diabetes, the adjusted OR for cavitary or sputum smear-positive TB was 1.7 and 1.5, respectively (95% CIs 1.5 to 1.8 and 1.4 to 1.6). Patients with TB and diabetes had 30% greater odds of dying and took longer to achieve negative Mycobacterium tuberculosis cultures and complete treatment., Conclusions: The prevalence of reported diabetes among adults with TB disease has increased. Having diabetes as a comorbidity negatively affects patient outcomes. In accordance with national recommendations, all patients aged ≥45 years and all younger patients who have risk factors for diabetes should be screened for diabetes at the start of TB treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The US Centers for Disease Control and Prevention recommends screening populations at increased risk for tuberculosis (TB), including persons born in countries with high TB rates. This approach assumes that TB risk for expatriates living in the United States is representative of TB risk in their countries of birth. We compared US TB rates by country of birth with corresponding country rates by calculating incidence rate ratios (IRRs) (World Health Organization rate/US rate). The median IRR was 5.4. The median IRR was 0.5 for persons who received a TB diagnosis <1 year after US entry, 4.9 at 1 to <10 years, and 10.0 at >10 years. Our analysis suggests that World Health Organization TB rates are not representative of TB risk among expatriates in the United States and that TB testing prioritization in the United States might better be based on US rates by country of birth and years in the United States.

OBJECTIVE: To determine risk factors for multidrug-resistant tuberculosis (MDR-TB) and describe MDR-TB according to three characteristics: previous TB disease, recent transmission of MDR-TB, and reactivation of latent MDR-TB infection. SETTING and DESIGN: We used 2011-2016 surveillance data from the US National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service and used logistic regression models to estimate risk factors associated with MDR-TB. RESULTS: A total of 615/45 209 (1.4%) cases were confirmed as MDR-TB; 111/615 (18%) reported previous TB disease; 41/615 (6.7%) were attributed to recent MDR-TB transmission; and 449/615 (73%) to reactivation. Only 12/41 (29%) patients with TB attributed to recent transmission were known to be contacts of someone with MDR-TB. For non-US-born patients, the adjusted odds ratios of having MDR-TB were 32.6 (95%CI 14.6-72.6) among those who were known to be contacts of someone with MDR-TB and 6.5 (95%CI 5.1-8.3) among those who had had previous TB disease. CONCLUSION: The majority of MDR-TB cases in the United States were associated with previous TB disease or reactivation of latent MDR-TB infection; only a small proportion of MDR-TB cases were associated with recent transmission.

We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system.

The U.S. Centers for Disease Control and Prevention (CDC) uses a combination of spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) analyses as part of the National TB Genotyping Service (NTGS). The NTGS expansion from 12-locus MIRU-VNTR (MIRU12) to 24-locus MIRU-VNTR (MIRU24) in 2009 enhanced the ability to discriminate Mycobacterium tuberculosis strains. In the current study, we investigated the MIRU24 concordance among epidemiologic-linked tuberculosis (TB) patients in four U.S. health jurisdictions. We also evaluated the programmatic benefits of combining MIRU24 and spoligotyping with epidemiologic evidence in identifying potential recent TB transmission. We examined 342 TB patients in 42 spoligotype/MIRU12 (PCRType) clusters (equivalent to 46 spoligotype/MIRU24 [GENType] clusters) to identify epidemiologic links among cases. GENType clusters, when compared to PCRType clusters, had 12 times higher odds of epidemiologic links being identified if patients were younger than 25 years and 3 times higher odds if patients resided in the same zip code, or had HIV infection. Sixty (18%) fewer PCRType-clustered patients would need investigations if clusters are defined using GENType instead of PCRType. An important advantage of defining clusters by MIRU24 is resource savings related to the reduced number of clustered cases needing investigation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Treatment completion is the cornerstone of tuberculosis (TB) control strategy globally. Although the majority of reported TB cases in the U.S. have documented treatment completion, individuals diagnosed while incarcerated are less likely to have documentation of whether or not they completed treatment. This study assessed trends and correlates of no documented treatment completion among individuals incarcerated at diagnosis., Methods: U.S. National TB Surveillance System (1999-2011) data on cases eligible for treatment completion were analyzed during 2014-2015. Treatment outcomes and trends in no documented completion were assessed by incarceration status. Multivariable logistic regression identified correlates of no documented completion among people incarcerated at diagnosis., Results: A lower proportion of individuals incarcerated at diagnosis had documented TB treatment completion than non-incarcerated individuals (75.6% vs 93.7%), and a higher proportion were lost to follow-up (10.7% vs 2.2%) or moved (9.4% vs 2.3%) during treatment (p<0.001). The 1999-2011 trend in no documented completion significantly increased among those incarcerated at diagnosis and declined among non-incarcerated individuals. Being foreign born was the strongest correlate of no documented completion among people incarcerated at diagnosis (AOR=2.86, 95% CI= 2.35, 3.49). Social risk factors for TB (e.g., homelessness, substance abuse), although common among incarcerated individuals, did not emerge as correlates of no documented completion., Conclusions: People diagnosed with TB disease at U.S. correctional facilities, especially the foreign born, require enhanced strategies for documenting TB treatment completion. Strengthened collaboration between correctional and public health agencies could improve continuity of care among released inmates., (Published by Elsevier Inc.)

Background: Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation., Methods: The study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC's National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study's CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1-3) was conducted using logistic regression., Results: Forty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters., Conclusions: We validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.

Tuberculosis is an infectious disease that may result from recent transmission or from an infection acquired many years in the past; there is no diagnostic test to distinguish the two causes. Cases resulting from recent transmission are particularly concerning from a public health standpoint. To describe recent tuberculosis transmission in the United States, we used a field-validated plausible source-case method to estimate cases likely resulting from recent transmission during January 2011-September 2014. We classified cases as resulting from either limited or extensive recent transmission based on transmission cluster size. We used logistic regression to analyze patient characteristics associated with recent transmission. Of 26,586 genotyped cases, 14% were attributable to recent transmission, 39% of which were attributable to extensive recent transmission. The burden of cases attributed to recent transmission was geographically heterogeneous and poorly predicted by tuberculosis incidence. Extensive recent transmission was positively associated with American Indian/Alaska Native (adjusted prevalence ratio [aPR] = 3.6 (95% confidence interval [CI] 2.9-4.4), Native Hawaiian/Pacific Islander (aPR = 3.2, 95% CI 2.3-4.5), and black (aPR = 3.0, 95% CI 2.6-3.5) race, and homelessness (aPR = 2.3, 95% CI 2.0-2.5). Extensive recent transmission was negatively associated with foreign birth (aPR = 0.2, 95% CI 0.2-0.2). Tuberculosis control efforts should prioritize reducing transmission among higher-risk populations.

Setting: Even among persons who have completed a course of treatment for their first tuberculosis (TB) episode, patients with a history of TB are at higher risk for having TB., Objective: To describe factors from the initial TB episode associated with recurrent TB among patients who completed treatment and remained free of TB for at least 12 months., Design: During 1993-2006, US TB cases stratified by birth origin were examined. Cox proportional hazards regression was used to assess the association of factors during the initial episode with recurrence at least 12 months after treatment completion., Results: Among 632 US-born patients, TB recurrence was associated with age 25-44 years (adjusted hazard ratio [aHR] 1.77, 99% confidence interval [CI] 1.02-3.09, attributable fraction [AF] 1-34%), substance use (aHR 1.57, 99%CI 1.23-2.02, AF 8-22%), and treatment supervised by health departments (aHR 1.42, 99%CI 1.03-1.97, AF 2-28%). Among 211 foreign-born patients, recurrence was associated with human immunodeficiency virus infection (aHR 2.24, 99%CI 1.27-3.98, AF 2-9%) and smear-positive TB (aHR 1.56, 99%CI 1.06-2.30, AF 3-33%)., Conclusion: Factors associated with recurrence differed by origin of birth, and might be useful for anticipating greater risk for recurrent TB among certain patients with a history of TB., Competing Interests: We declare that we have no conflicts of interest.

Tuberculosis genotyping data are frequently used to estimate the proportion of tuberculosis cases in a population that are attributable to recent transmission (RT). Multiple factors influence genotype-based estimates of RT and limit the comparison of estimates over time and across geographic units. Additionally, methods used for these estimates have not been validated against field-based epidemiologic assessments of RT. Here we describe a novel genotype-based approach to estimation of RT based on the identification of plausible-source cases, which facilitates systematic comparisons over time and across geographic areas. We compared this and other genotype-based RT estimation approaches with the gold standard of field-based assessment of RT based on epidemiologic investigation in Arkansas, Maryland, and Massachusetts during 1996-2000. We calculated the sensitivity and specificity of each approach for epidemiologic evidence of RT and calculated the accuracy of each approach across a range of hypothetical RT prevalence rates plausible for the United States. The sensitivity, specificity, and accuracy of genotype-based RT estimates varied by approach. At an RT prevalence of 10%, accuracy ranged from 88.5% for state-based clustering to 94.4% with our novel approach. Our novel, field-validated approach allows for systematic assessments over time and across public health jurisdictions of varying geographic size, with an established level of accuracy., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We estimated the rate of reactivation tuberculosis (TB) in the United States, overall and by population subgroup, using data on TB cases and Mycobacterium tuberculosis isolate genotyping reported to the Centers for Disease Control and Prevention during 2006-2008. The rate of reactivation TB was defined as the number of non-genotypically clustered TB cases divided by the number of person-years at risk for reactivation due to prevalent latent TB infection (LTBI). LTBI was ascertained from tuberculin skin tests given during the 1999-2000 National Health and Nutrition Examination Survey. Clustering of TB cases was determined using TB genotyping data collected by the Centers for Disease Control and Prevention and analyzed via spatial scan statistic. Of the 39,920 TB cases reported during 2006-2008, 79.7% were attributed to reactivation. The overall rate of reactivation TB among persons with LTBI was estimated as 0.084 (95% confidence interval (CI): 0.083, 0.085) cases per 100 person-years. Rates among persons with and without human immunodeficiency virus coinfection were 1.82 (95% CI: 1.74, 1.89) and 0.073 (95% CI: 0.070, 0.075) cases per 100 person-years, respectively. The rate of reactivation TB among persons with LTBI was higher among foreign-born persons (0.098 cases/100 person-years; 95% CI: 0.096, 0.10) than among persons born in the United States (0.082 cases/100 person-years; 95% CI: 0.080, 0.083). Differences in rates of TB reactivation across subgroups support current recommendations for targeted testing and treatment of LTBI.

The United States-Affiliated Pacific Islands (USAPI) are part of the US National Tuberculosis (TB) Surveillance System and use laboratory services contracted through a cooperative agreement with the Centers for Disease Control and Prevention (CDC). In 2004, the CDC established the National Tuberculosis Genotyping Service, a system to genotype 1 isolate from each culture-confirmed case of TB. To describe the molecular epidemiology of TB in the region, we examined all Mycobacterium tuberculosis isolates submitted for genotyping from January 1, 2004, to December 31, 2008. Over this time period, the USAPI jurisdictions reported 1339 verified TB cases to the National Tuberculosis Surveillance System. Among 419 (31%) reported culture-confirmed TB cases, 352 (84%) had complete genotype results. Routine TB genotyping allowed, for the first time, an exploration of the molecular epidemiology of TB in the USAPI.

Objectives: 1) To describe homeless persons diagnosed with tuberculosis (TB) during the period 1994-2010, and 2) to estimate a TB incidence rate among homeless persons in the United States., Methods: TB cases reported to the National Tuberculosis Surveillance System were analyzed by origin of birth. Incidence rates were calculated using the US Department of Housing and Urban Development homeless population estimates. Analysis of genotyping results identified clustering as a marker for transmission among homeless TB patients., Results: Of 270,948 reported TB cases, 16,527 (6%) were homeless. The TB incidence rate among homeless persons ranged from 36 to 47 cases per 100,000 population in 2006-2010. Homeless TB patients had over twice the odds of not completing treatment and of belonging to a genotype cluster. US- and foreign-born homeless TB patients had respectively 8 and 12 times the odds of substance abuse., Conclusions: Compared to the general population, homeless persons had an approximately 10-fold increase in TB incidence, were less likely to complete treatment and more likely to abuse substances. Public health outreach should target homeless populations to reduce the excess burden of TB in this population., Competing Interests: Conflicts of Interest: None declared.

Background: Early identification of outbreaks remains a key component in continuing to reduce the burden of infectious disease in the United States. Previous studies have applied statistical methods to detect unexpected cases of disease in space or time. The objectives of our study were to assess the ability and timeliness of three spatio-temporal methods to detect known outbreaks of tuberculosis., Methods: We used routinely available molecular and surveillance data to retrospectively assess the effectiveness of three statistical methods in detecting tuberculosis outbreaks: county-based log-likelihood ratio, cumulative sums, and a spatial scan statistic., Results: Our methods identified 8 of the 9 outbreaks, and 6 outbreaks would have been identified 1-52 months (median=10 months) before local public health authorities identified them. Assuming no delays in data availability, 46 (59.7%) of the 77 patients in the 9 outbreaks were identified after our statistical methods would have detected the outbreak but before local public health authorities became aware of the problem., Conclusions: Statistical methods, when applied retrospectively to routinely collected tuberculosis data, can successfully detect known outbreaks, potentially months before local public health authorities become aware of the problem. The three methods showed similar results; no single method was clearly superior to the other two. Further study to elucidate the performance of these methods in detecting tuberculosis outbreaks will be done in a prospective analysis.

Recurrent tuberculosis (TB) can result from reactivation of a previous TB episode or reinfection with a new Mycobacterium tuberculosis strain. A retrospective analysis of all recurrent TB cases reported in the United States during 1993-2010 was conducted. The proportion of recurrent cases remained stable during the study period (annual range 4.2-5.7%). Compared with persons without a previous diagnosis of TB, persons with recurrent TB experienced lower treatment completion within 12 months and higher mortality during the recurrent episode. Persons with recurrent TB have poorer outcomes, suggesting the need for targeted interventions to ensure treatment completion.

To determine the proportion of reported tuberculosis (TB) cases due to recent transmission in the United States, we conducted a cross-sectional study to examine culture-positive TB cases with complete genotype results (spoligotyping and 12-locus mycobacterial interspersed repetitive unit-variable-number tandem repeat typing) reported during January 2005-December 2009. Recently transmitted cases were defined as cases with matching results reported within statistically significant geospatial zones (identified by a spatial span statistic within a sliding 3-year window). Approximately 1 in 4 TB cases reported in the United States may be attributed to recent transmission. Groups at greatest risk for recent transmission appear to be men, persons born in the United States, members of a minority race or ethnic group, persons who abuse substances, and the homeless. Understanding transmission dynamics and establishing strategies for rapidly detecting recent transmission among these populations are essential for TB elimination in the United States.

We combined routinely reported tuberculosis (TB) patient characteristics with genotyping data and measures of geospatial concentration to predict which small clusters (i.e., consisting of only 3 TB patients) in the United States were most likely to become outbreaks of at least 6 TB cases. Of 146 clusters analyzed, 16 (11.0%) grew into outbreaks. Clusters most likely to become outbreaks were those in which at least 1 of the first 3 patients reported homelessness or excess alcohol or illicit drug use or was incarcerated at the time of TB diagnosis and in which the cluster grew rapidly (i.e., the third case was diagnosed within 5.3 months of the first case). Of 17 clusters with these characteristics and therefore considered high risk, 9 (53%) became outbreaks. This retrospective cohort analysis of clusters in the United States suggests that routinely reported data may identify small clusters that are likely to become outbreaks and which are therefore candidates for intensified contact investigations.

Background: Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB., Methods: We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred., Results: The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P < .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission., Conclusions: Our assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States.

Objectives: To describe older adults with tuberculosis (TB) and compare demographic, diagnostic, and disease characteristics and treatment outcomes between older and younger adults with TB., Design: Descriptive analysis of all confirmed people with TB aged 21 and older., Setting: The National Tuberculosis Surveillance System (NTSS) for the 50 United States and the District of Columbia from 1993 to 2008., Participants: A total of 250,784 adult TB cases were reported, including 61,119 people with TB aged 65 and older., Measurements: TB case count and rates and proportion of TB cases in older adults., Results: Older adults had consistently higher incidence rates of TB than younger adults. In 2008, the rate of TB in older adults was 6.4 per 100,000, compared with 5.0 per 100,000 for younger adults. A lower percentage of older adults had TB diagnostic test results (tuberculin skin test, sputum smear, sputum culture) or human immunodeficiency virus (HIV) infection status reported. TB risk factors (substance use, homelessness, HIV infection) and multidrug-resistant TB were less prevalent in older than younger adults. Seven percent of older adults were dead at diagnosis, and 21% died during therapy, compared with 2% and 7%, respectively, of younger adults. Sputum culture conversion percentages were similar for people who did not die. Older adults also completed therapy in a timely manner, similar to younger adults., Conclusion: Although older adults had higher rates of TB and mortality, for older adults who survived therapy, successful treatment outcomes were similar to those of younger adults., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Background: The true burden of reactivation of remote latent tuberculosis infection (reactivation TB) among foreign-born persons with tuberculosis (TB) within the United States is not known. Our study objectives were to estimate the proportion of foreign-born persons with TB due reactivation TB and to describe characteristics of foreign-born persons with reactivation TB., Methods: We conducted a cross-sectional study of patients with an M. tuberculosis isolate genotyped by the U.S. National TB Genotyping Service, 2005-2009. TB cases were attributed to reactivation TB if they were not a member of a localized cluster of cases. Localized clusters were determined by a spatial scan statistic of cases with isolates with matching TB genotype results. Crude odds ratios and 95% confidence intervals were used to assess relations between reactivation TB and select factors among foreign-born persons., Main Results: Among the 36,860 cases with genotyping and surveillance data reported, 22,151 (60%) were foreign-born. Among foreign-born persons with TB, 18,540 (83.7%) were attributed to reactivation TB. Reactivation TB among foreign-born persons was associated with increasing age at arrival, incidence of TB in the country of origin, and decreased time in the U.S. at the time of TB diagnosis., Conclusions: Four out of five TB cases among foreign-born persons can be attributed to reactivation TB and present the largest challenge to TB elimination in the U.S. TB control strategies among foreign-born persons should focus on finding and treating latent tuberculosis infection prior to or shortly after arrival to the United States and on reducing the burden of LTBI through improvements in global TB control.

Background: Tuberculosis (TB) control efforts are often ineffective in controlling TB among patients who use illicit drugs or abuse alcohol (substance abuse). This study examined the prevalence of substance abuse among TB cases reported in the United States and assessed the relation between substance abuse and indicators of TB transmission., Methods: A cross-sectional analysis was performed of data on US TB cases in patients 15 years or older reported from 1997 through 2006. Analyses included number and proportion of patients with TB characterized by substance abuse and associations between substance abuse, sputum smear status, treatment failure, and inclusion in a county-level genotype cluster., Results: Of 153,268 patients with TB, 28,650 (18.7%) reported substance abuse, including 22,293 of 76,816 US-born patients (29.0%). Multivariate analysis showed that, among patients negative for human immunodeficiency virus, odds of sputum smear-positive disease were 1.8 (99% confidence interval [CI], 1.7-1.9) times greater among those who reported substance abuse; this association was weaker among patients with human immunodeficiency virus infection (odds ratio [OR], 1.2; 99% CI, 1.1-1.4). Among female patients, odds of treatment failure were 2.4 (99% CI, 1.9-3.0) times greater among those who reported substance abuse. The association was weaker among male patients (OR, 1.5; 99% CI, 1.3-1.7). Patients who abused substances were more likely to be involved in a county-level genotype cluster (US-born: OR, 2.3; 99% CI, 2.0-2.7; foreign-born: 1.5; 1.2-2.0)., Conclusions: Substance abuse is the most commonly reported behavioral risk factor among patients with TB in the United States. Patients who abuse substances are more contagious (eg, smear positive) and remain contagious longer because treatment failure presumably extends periods of infectiousness. Increased transmission is consistent with our finding that patients who abuse substances were more likely to be involved in a localized genotype cluster, which can represent recent transmission.

Background: Seven percent of tuberculosis (TB) cases reported to the US National Tuberculosis Surveillance System in 2005 had Mycobacterium tuberculosis isolates with resistance to at least isoniazid., Methods: We undertook this study to describe demographic characteristics, risk factor information, and treatment outcomes for persons with isoniazid-monoresistant (resistant to isoniazid and susceptible to rifampin, pyrazinamide, and ethambutol hydrochloride) TB compared with persons with TB susceptible to all first-line anti-TB drugs., Results: The numbers of isoniazid-monoresistant TB cases increased from 303 (4.1%) in 1993 to 351 (4.2%) in 2005. In our multivariate analysis of all TB cases reported from 1993 to 2003, the races/ethnicities of patients with isoniazid-monoresistant TB were significantly more likely to be US-born Asian/Pacific Islander (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.4-2.6), foreign-born Asian/Pacific Islander (1.8; 1.4-2.1), foreign-born black non-Hispanic (1.4; 1.1-1.7), or US-born Hispanic (1.3; 1.1-1.5). Isoniazid monoresistance was also associated with failure to complete therapy within 1 year (aOR, 1.7; 95% CI, 1.5-1.8), a history of TB (1.5; 1.3-1.7), and correctional facility residence (1.5; 1.2-1.7)., Conclusions: Isoniazid-monoresistant TB did not decline from January 1, 1993, through December 31, 2005, despite national downward trends observed in overall TB cases and in multidrug-resistant TB cases. Physicians must ensure completion of treatment for patients taking isoniazid as part of their TB or latent TB infection therapy. In addition, physicians should maintain heightened vigilance for isoniazid resistance when evaluating certain at-risk populations for TB and latent TB infection.

Background: Understanding the epidemiology of human Mycobacterium bovis tuberculosis (TB) in the United States is imperative; this disease can be foodborne or airborne, and current US control strategies are focused on TB due to Mycobacterium tuberculosis and airborne transmission. The National TB Genotyping Service's work has allowed systematic identification of M. tuberculosis-complex isolates and enabled the first US-wide study of M. bovis TB., Methods: Results of spacer oligonucleotide and mycobacterial interspersed repetitive units typing were linked to corresponding national surveillance data for TB cases reported for the period 2004-2005 and select cases for the period 1995-2003. We also used National TB Genotyping Service data to evaluate the traditional antituberculous drug resistance-based case definition of M. bovis TB., Results: Isolates from 165 (1.4%) of 11,860 linked cases were identified as M. bovis. Patients who were not born in the United States, Hispanic patients, patients <15 years of age, patients reported to be HIV infected, and patients with extrapulmonary disease each had increased adjusted odds of having M. bovis versus M. tuberculosis TB. Most US-born, Hispanic patients with TB due to M. bovis (29 [90.6%] of 32) had extrapulmonary disease, and their overall median age was 9.5 years. The National TB Genotyping Service's data indicated that the pyrazinamide-based case definition's sensitivity was 82.5% (95% confidence interval; 75.3%-87.9%) and that data identified 14 errors in pyrazinamide-susceptibility testing or reporting., Conclusions: The prevalence of extrapulmonary disease in the young, US-born Hispanic population suggests recent transmission of M. bovis, possibly related to foodborne exposure. Because of its significantly different epidemiologic profile, compared with that of M. tuberculosis TB, we recommend routine surveillance of M. bovis TB. Routine surveillance and an improved understanding of M. bovis TB transmission dynamics would help direct the development of additional control measures.

Context: Appalachia has been characterized by its poverty, a factor associated with tuberculosis, yet little is known about the disease in this region., Purpose: To determine whether Appalachian tuberculosis risk factors, trends, and rates differ from the rest of the United States., Methods: Analysis of tuberculosis cases reported to the Centers for Disease Control and Prevention's National Tuberculosis Surveillance System (NTSS) within the 50 states and the District of Columbia from 1993 through 2005., Results: The 2005 rate of tuberculosis in rural Appalachia was 2.1/100,000, compared to 2.7/100,000 in urban Appalachia. Urban non-Appalachia had a 2005 tuberculosis rate of 5.4/100,000. Over the 13-year period, tuberculosis rates fell in Appalachia at an annual rate of 7.8%. In one age group (15- to 24-year-olds) the rates increased at an annual rate of 2.8%. Foreign-born Hispanics were the largest racial/ethnic group in this age group. When private providers gave exclusive care for tuberculosis disease, Appalachians were less likely to complete therapy in a timely manner when compared to non-Appalachians (OR 0.6, 95% CI 0.5-0.7)., Conclusions: Tuberculosis rates and trends are similar in urban and rural Appalachia. It is crucial for public health officials in Appalachia to address the escalating TB rate among 15- to 24-year-olds by focusing prevention efforts on the growing numbers of foreign-born cases. Due to the increased risk of treatment failure among Appalachians who do not seek care from the health department, public health authorities must ensure completion of treatment for patients who seek private providers.

Background: Patients with tuberculosis (TB) in the United States are often described in 2 broad categories, US-born and foreign-born, which may mask differences among different immigrant groups. We determined characteristics of patients born in South Asia and diagnosed as having TB in the United States., Methods: All 224,101 TB cases reported to the US National Tuberculosis Surveillance System from the 50 states and the District of Columbia from 1993 to 2004 were included. We used descriptive analysis and logistic regression to explore differences among patients born in South Asia, other foreign-born, and US-born TB patients., Results: Half of the South Asian TB patients (50.5%) in our study were in the 25- to 44-year-old age group, compared with 40.1% of other foreign-born TB patients and 31.8% of US-born TB patients. Compared with other foreign-born TB patients, South Asians were more likely to have extrapulmonary disease (odds ratio [OR], 1.7), more likely to be uninfected with human immunodeficiency virus (HIV) (OR, 5.8) but also more likely not to be offered HIV testing (OR, 9.4) or not to accept an HIV test if offered (OR, 11.8), and more likely not to be homeless (OR, 2.9) or not to use drugs or excess alcohol (OR, 2.7)., Conclusions: South Asian TB patients in the United States are younger and more commonly develop extrapulmonary TB than other foreign-born patients. New TB control strategies that target younger patients and that encourage HIV testing and inform physicians about high extrapulmonary TB in the absence of common risk factors in South Asians are needed.

Background: To our knowledge, this is the first assessment of trends in tuberculosis (TB)/human immunodeficiency virus (HIV) comorbidity in the United States based on national TB surveillance data., Methods: We analyzed all incident TB cases reported to the Centers for Disease Control and Prevention national TB surveillance system from all 50 states and the District of Columbia from 1993 through 2004. Trends in TB/HIV cases were examined according to selected demographic and clinical characteristics., Results: Cases of TB/HIV decreased from 3681 (15% of 25,108 TB cases) in 1993 to 1187 (8% of 14,515 TB cases) in 2004, accounting for 23% of the overall decrease in TB cases during this period. The TB/HIV case rate decreased from 1.4/100,000 in 1993 to 0.4/100,000 in 2004. The highest TB/HIV comorbidity rates persisted in persons aged 25 to 44 years (13.8%), males (9.7%), US-born persons (10.7%), non-Hispanic blacks (17.8%), and persons from the Northeast (11.0%) and the South (10.1%). Propensity stratification, used to account for the unequal probability of patients with TB being tested for HIV during the study period, did not show important differences in TB/HIV comorbidity trends., Conclusions: Comorbidity due to TB/HIV decreased substantially between 1993 and 2004, primarily in US-born persons in states that experienced a TB resurgence between 1985 and 1992. These decreases coincide with improvements in TB control and advances in HIV treatment and diagnosis. The overall decreases obscure the wide variation in comorbidity that exists among some demographic groups and the recent slowing in the decline over the past 3 years.

Background: Tuberculosis (TB) transmission in nontraditional settings and relationships (non-TSR) often eludes detection by conventional contact investigation and is increasingly common. The U.S.-based National Tuberculosis Genotyping and Surveillance Network collected epidemiologic data and genotyping results of Mycobacterium tuberculosis isolates from 1996 to 2000., Methods: In 2003-2004, we determined the number and characteristics of TB patients in non-TSR that were involved in recent transmission, generated a decision tree to profile those patients, and performed a case-control study to identify predictors of being in non-TSR., Results: Of 10,844 culture-positive reported TB cases that were genotyped, 4724 (43.6%) M. tuberculosis isolates were clustered with at least one other isolate. Among these, 520 (11%) had epidemiologic linkages discovered during conventional contact investigation or cluster investigation and confirmed by genotyping results. The decision tree identified race/ethnicity (non-Hispanic white or black) as having the greatest predictive ability to determine patients in non-TSR, followed by being aged 15 to 24 years and having positive or unknown HIV infection status. From the 520, 85 (16.4%) had non-TSR, and 435 (83.6%) had traditional settings and relationships (TSR). In multivariate analyses, patients in non-TSR were significantly more likely than those in TSR to be non-Hispanic white (adjusted odds ratio [aOR]=6.1; 95% confidence interval [CI]=1.7-21.1]) or to have an M. tuberculosis isolate resistant to rifampin (aOR=5.2; 95% CI=1.5-17.7)., Conclusions: Decision-tree analyses can be used to enhance both the efficiency and effectiveness of TB prevention and control activities in identifying patients in non-TSR.

The Centers for Disease Control and Prevention established the US National Tuberculosis Genotyping and Surveillance Network to study the utility of genotyping Mycobacterium tuberculosis isolates for prevention and control. From 1998 to 2000, four sites performed conventional contact investigations and epidemiologic investigations of cases with genotypically matched M. tuberculosis isolates, called cluster investigations. The authors compared cluster pairs (two cases with M. tuberculosis isolates having identical genotypes) whose epidemiologic linkages were discovered only during cluster investigation with those whose epidemiologic linkages were discovered during conventional contact investigation. Among the 2,141 reported culture-positive tuberculosis cases, 2,055 (96%) M. tuberculosis isolates were genotyped. By itself and at a minimum, cluster investigation added 43 (38%) of the 113 total epidemiologic linkages discovered. Of the epidemiologic linkages discovered during conventional contact investigation, 29% of tuberculosis case pairs were not supported by genotyping data. The linkages discovered only during cluster investigation were more likely discovered in nontraditional settings and relationships and among larger clusters (cluster size of >5: adjusted odds ratio = 57.6, 95% confidence interval: 31.8, 104.6). Information gained from genotyping M. tuberculosis isolates should initiate cluster investigations of tuberculosis cases not previously discovered as being epidemiologically linked during conventional contact investigation. Cluster investigations will play a crucial role in predicting recent tuberculosis transmission more accurately, as we move toward tuberculosis elimination in the United States.

DNA fingerprinting was used to evaluate epidemiologically linked case pairs found during routine tuberculosis (TB) contact investigations in seven sentinel sites from 1996 to 2000. Transmission was confirmed when the DNA fingerprints of source and secondary cases matched. Of 538 case pairs identified, 156 (29%) did not have matching fingerprints. Case pairs from the same household were no more likely to have confirmed transmission than those linked elsewhere. Case pairs with unconfirmed transmission were more likely to include a smear-negative source case (odds ratio [OR] 2.0) or a foreign-born secondary case (OR 3.4) and less likely to include a secondary case <15 years old (OR 0.3). Our study suggests that contact investigations should focus not only on the household but also on all settings frequented by an index case. Foreign-born persons with TB may have been infected previously in high-prevalence countries; screening and preventive measures recommended by the Institute of Medicine could prevent TB reactivation in these cases.