Outbreak investigation is an essential component of tuberculosis (TB) control in the United States, but its epidemiologic impact and cost-effectiveness have not been quantified. We modeled outbreak investigation activities in the United States during 2023-2032 and estimated corresponding epidemiologic impact, economic costs (in 2022 US$), and incremental cost-effectiveness ratios from the healthcare system perspective (cost per additional quality-adjusted life-year gained). We projected that outbreak investigations would result in 1,030,000 (95% uncertainty interval [UI] 376,000-1,740,000) contacts investigated, leading to 4,130 (95% UI 1,420-7,640) TB diagnoses and 104,000 (95% UI 37,600-181,000) latent TB infection diagnoses, at a total cost of US $219 million (95% UI $80-$387 million). We estimated that 5,560 (95% UI 1,720-11,400) TB cases would be averted through early detection and treatment, and the incremental cost-effectiveness of outbreak investigations, compared with no outbreak investigations, was $27,800 per quality-adjusted life-year gained (95% UI $4,580-$68,700).

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.

<sec id="st1"><title>BACKGROUND</title>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.</sec><sec id="st2"><title>METHODS</title>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.</sec><sec id="st3"><title>RESULTS</title>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).</sec><sec id="st4"><title>CONCLUSIONS</title>Inability to obtain sputum from children and higher diagnostic suspicion for disease processes that require tissue-based diagnostics could explain these findings.</sec>.

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.

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.

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.

INTRODUCTION: In 2020, the COVID-19 pandemic led to significant declines in cancer screening, including among women served by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This study examined the spatial association between state-based COVID-19 test percent positivity and proportional change in NBCCEDP screening volume. METHODS: Using the COVID-19 Diagnostic Laboratory Testing dataset, we calculated state-based monthly COVID-19 test percent positivity from July through December 2020 and categorized rates into low, medium, and high groups. We used data from 48 NBCCEDP state awardees to calculate the state-based monthly proportional change in screening volume and compared data for July-December 2020 with the previous 5-year average for those months. We categorized changes in screening volume into large decrease, medium decrease, and minimal change and created maps of the associations between variable subgroups by using bivariate mapping in QGIS. RESULTS: Bivariate relationships between COVID-19 test percent positivity and proportional change in cancer screening volume varied over time and geography. In 5 of 6 months, 4 states had high COVID-19 test percent positivity and minimal change in breast or cervical cancer screening volume; 2 states had high COVID-19 test percent positivity and minimal change in breast and cervical cancer screening volume. CONCLUSION: Some states maintained pre-COVID-19 screening volumes despite high COVID-19 test percent positivity. Follow-up research will be conducted to determine how these states differ from those with consistent decreases in screening volume and identify factors that may have contributed to differences. This information could be useful for planning to maximize NBCCEDP awardees' ability to maintain screening volume during future public health emergencies.

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.

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: 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 CDC during 2012-2016 in the United States and separately in California, Florida, New York, and Texas. Using these models, we estimated the mean number of secondary cases generated per infectious case (R0) and individual-level heterogeneity in R0 at state and national levels. We also assessed how different definitions of clustering and variation in case ascertainment affected these estimates. RESULTS: In clusters of genotypically linked TB cases occurring within a state over a 5-year period (reference scenario), the estimated R0 was 0.29 (95% CI: 0.28-0.31) 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 (0.15-0.17) 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 (0.3-0.4) in California, 0.28 (0.24-0.36) in Florida, 0.19 (0.15-0.27) in New York, and 0.38 (0.33-0.46) 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 in the United States and worldwide.

BACKGROUND: Recent evidence suggests transmission of Mycobacterium tuberculosis (Mtb) may be characterized by extreme individual heterogeneity in secondary cases (i.e., few cases account for the majority of transmission). Such heterogeneity implies outbreaks are rarer but more extensive and has profound implications in infectious disease control. However, discrete person-to-person transmission events in TB are often unobserved, precluding our ability to directly quantify individual heterogeneity in TB epidemiology. METHODS: We used a modified negative binomial branching process model to quantify the extent of individual heterogeneity using only observed transmission cluster size distribution data (i.e., the simple sum of all cases in a transmission chain) without knowledge of individual-level transmission events. The negative binomial parameter k quantifies the extent of individual heterogeneity (generally, k<1 indicates extensive heterogeneity, and as k→∞ transmission becomes more homogenous). We validated the robustness of the inference procedure considering common limitations affecting cluster-size data. Finally, we demonstrate the epidemiologic utility of this method by applying it to aggregate United States molecular surveillance data from the U.S. Centers for Disease Control and Prevention. RESULTS: The cluster-based method reliably inferred k using TB transmission cluster data despite a high degree of bias introduced into the model. We found that the TB transmission in the United States was characterized by a high propensity for extensive outbreaks (k=0.09; 95% confidence interval: 0.09, 0.10). CONCLUSION: The proposed method can accurately quantify critical parameters that govern TB transmission using simple, more easily obtainable cluster data to improve our understanding of TB epidemiology.

Sputum-culture confirmation guides tuberculosis (TB) diagnosis and patient management but has previously been reported to be low in the US-Affiliated Pacific Islands (USAPI). We evaluated factors associated with positive sputum-culture results by analyzing TB case surveillance and laboratory data, including sputa quality and quantity for diagnostic specimens from the USAPI. A lower proportion of sputum specimens were reported as culture positive from the USAPI (42%), compared with Hawaii (58%) and the United States (55%). Few (3%) sputa collected from TB patients in the USAPI had both optimal quality and quantity; 40% had optimal quality (mucoid), and 7% had optimal quantity (>5 mL). Suboptimal sputum specimen quality and quantity contributed to fewer sputum-culture positive results in the USAPI. Improving sputum collection and handling might lead to more culture positive results and ultimately improve patient care and TB control in USAPI.

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.

BACKGROUND: Older age is a risk factor for TB in low incidence settings. Using data from the U.S. 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: 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 8.34-9.23) in 51-year-olds to 4.51% (3.87-5.14) in 90-year-olds. Controlling for age, incidence rates were lower for more recent birth cohorts, dropping 8.79% (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.

Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2-69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation. Code available at: https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171.

Women from racial and ethnic minority groups face a disproportionate burden of cervical and breast cancers in the United States. The Coronavirus Disease 2019 (COVID-19) pandemic might exacerbate these disparities as supply and demand for screening services are reduced. The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides cancer screening services to women with low income and inadequate health insurance. We examined COVID-19's impact on NBCCEDP screening services during January-June 2020. We found the total number of NBCCEDP-funded breast and cervical cancer screening tests declined by 87% and 84%, respectively, during April 2020 compared with the previous 5-year averages for that month. The extent of declines varied by geography, race/ethnicity, and rurality. In April 2020, screening test volume declined most severely in Health and Human Services Region 2 - New York (96% for breast, 95% for cervical cancer screening) compared to the previous 5-year averages. The greatest declines were among American Indian/Alaskan Native women for breast cancer screening (98%) and Asian Pacific Islander women for cervical cancer screening (92%). Test volume began to recover in May and, by June 2020, NBCCEDP breast and cervical cancer screening test volume was 39% and 40% below the 5-year average for that month, respectively. However, breast cancer screening remained over 50% below the 5-year average among women in rural areas. NBCCEDP programs reported assisting health care providers resume screening.

INTRODUCTION: In the U.S., universal genotyping of culture-confirmed tuberculosis cases facilitates cluster detection. Early recognition of the small clusters more likely to become outbreaks can help prioritize public health resources for immediate interventions. METHODS: This study used national surveillance data reported during 2009-2018 to describe incident clusters (≥3 tuberculosis cases with matching genotypes not previously reported in the same county); data were analyzed during 2020. Cox proportional hazards regression models were used to examine the patient characteristics associated with clusters doubling in size to ≥6 cases. RESULTS: During 2009-2018, a total of 1,516 incident clusters (comprising 6,577 cases) occurred in 47 U.S. states; 231 clusters had ≥6 cases. Clusters of ≥6 cases disproportionately included patients who used substances, who had recently experienced homelessness, who were incarcerated, who were U.S. born, or who self-identified as being of American Indian or Alaska Native race or of Black race. A median of 54 months elapsed between the first and the third cases in clusters that remained at 3-5 cases compared with a median of 9.5 months in clusters that grew to ≥6 cases. The longer time between the first and third cases and the presence of ≥1 patient aged ≥65 years among the first 3 cases predicted a lower hazard for accumulating ≥6 cases. CONCLUSIONS: Clusters accumulating ≥3 cases within a year should be prioritized for intervention. Effective response strategies should include plans for targeted outreach to U.S.-born individuals, incarcerated people, those experiencing homelessness, people using substances, and individuals self-identifying as being of American Indian or Alaska Native race or of Black race.

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.

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.

BACKGROUND: Persons living with HIV are more likely to have tuberculosis (TB) disease attributed to recent transmission (RT) and to die during TB treatment than persons without HIV. We examined factors associated with RT or mortality among TB/HIV patients. METHODS: Using National TB Surveillance System data from 2011 to 2016, we calculated multivariable adjusted odds ratios (aOR) with 99% confidence intervals (CI) to estimate associations between patient characteristics and RT or mortality. Mortality analyses were restricted to 2011-2014 to allow sufficient time for reporting outcomes. RESULTS: TB disease was attributed to RT in 491 (20%) of 2415 TB/HIV patients. RT was more likely among those reporting homelessness (aOR, 2.6; CI, 2.0, 3.5) or substance use (aOR,1.6; CI, 1.2, 2.1) and among blacks (aOR,1.8; CI, 1.2, 2.8) and Hispanics (aOR, 1.8; CI, 1.1, 2.9); RT was less likely among non-US-born persons (aOR, 0.2; CI, 0.2, 0.3). The proportion who died during TB treatment was higher among persons with HIV than without (8.6% versus 5.2%; p < 0.0001). Among 2273 TB/HIV patients, 195 died during TB treatment. Age >/= 65 years (aOR, 5.3; CI, 2.4, 11.6), 45-64 years (aOR, 2.2; CI, 1.4, 3.4), and having another medical risk factor for TB (aOR, 3.3; CI, 1.8, 6.2) were associated with death; directly observed treatment (DOT) for TB was protective (aOR, 0.5; CI, 0.2, 1.0). CONCLUSIONS: Among TB/HIV patients, blacks, Hispanics, and those reporting homelessness or substance use should be prioritized for interventions that decrease TB transmission. Improved adherence to treatment through DOT was associated with decreased mortality, but additional interventions are needed to reduce mortality among older patients and those TB/HIV patients with another medical risk factor for TB.

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.

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.

INTRODUCTION: Screening can decrease colorectal cancer incidence and mortality and is recommended in clinical practice guidelines. Poor quality of colorectal cancer screening can negate the benefit of screening. The objective of this study was to assess the quality of screening services provided by the Centers for Disease Control and Prevention's Colorectal Cancer Control Program from July 2009 through June 2015. METHODS: We collected data from the program's 29 grantees, funded to provide colorectal cancer screening and diagnostic services to asymptomatic, low-income, and underinsured or uninsured adults aged 50 to 64. We collected data on the dates and results of all screening and diagnostic tests and, for colonoscopies, on whether the cecum was reached, whether bowel preparation was adequate, and endoscopists' recommendations for the next test. RESULTS: Overall, 82.9% (range among grantees, 50.0%-97.2%) of positive FOBTs/FITs were followed up by colonoscopy; 95.2% of colonoscopies occurred within 180 days of the positive stool test. Cecal intubation rates ranged among grantees from 94.2% to 100%. Adenoma detection rates met recommended threshold levels for almost all grantees. Recommendations for rescreening and surveillance intervals deviated from guidelines in both directions. Of clients with normal colonoscopies, 85.3% (range, 37.7%-99.7%) were told to return in 10 years, as recommended in national guidelines. Of clients with advanced adenomas, 55.2% (range, 20.0%-84.6%) were told to return in 3 years as recommended, 25.4% (range, 3.8%-56.6%) in 5 or more years, and 18.6% (range, 0%-47.2%) in less than 3 years. CONCLUSION: Although overall screening quality was good, it varied considerably. Ongoing monitoring to identify performance problems is essential for all colorectal cancer screening activities, so that efforts designed to improve performance can be targeted to individual clinicians.

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.

Cancer is the second leading cause of death in the United States (1), and colorectal cancer (CRC) is the second leading cause of cancer death among cancers that affect both men and women (2). There is strong evidence that screening for CRC reduces incidence and mortality rates from the disease either by detecting cancer early, when treatments are more effective, or by preventing CRC through removal of precancerous polyps (3). The US Preventive Services Task Force recommends CRC screening for people at average risk (aged 50–75 y), using either stool-based tests (ie, fecal immunochemical test [FIT], fecal occult blood test [FOBT], multi-targeted stool DNA test [FIT-DNA]) or tests that directly visualize the colon (ie, colonoscopy, sigmoidoscopy, or computed tomographic colonography [CTC]) (3). Despite availability of these tests, a significant proportion of Americans remain unscreened; in 2016, only 67.3% of age-appropriate men and women were up to date with screening (4).

SETTING: Current guidelines recommend latent tuberculous infection (LTBI) testing at the time of human immunodeficiency virus (HIV) diagnosis and annually thereafter for persons at high risk of LTBI. OBJECTIVES: To estimate LTBI testing prevalence and describe the characteristics of HIV-infected persons who would benefit from annual LTBI testing. DESIGN: We estimated the proportions of LTBI testing among a nationally representative sample of HIV-infected adults in care between 2010 and 2012, and compared the patient characteristics of those with a positive LTBI test result to those with a negative result using chi2 tests. RESULTS: Among 2772 patients, 68.8% had been tested for LTBI at least once since HIV diagnosis, and 39.4% had been tested during the previous 12 months. Among patients tested at least once, 6.9% tested positive, 80.7% tested negative, and 12.4% had an indeterminate or undocumented result. Patients with a positive test were significantly more likely to be foreign-born, have lower educational attainment, and a household income at or below the federal poverty level. CONCLUSIONS: More than 30% of HIV-infected patients had never been tested for LTBI. Providers should test all patients for LTBI at the time of HIV diagnosis. The patient characteristics associated with a positive LTBI test result may guide provider decisions about annual testing.

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.

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.

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.