Disparities in Tuberculosis Incidence by Race and Ethnicity Among the U.S.-Born Population in the United States, 2011 to 2021 : An Analysis of National Disease Registry Data.

BACKGROUND: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. OBJECTIVE: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. DESIGN: Time-series analysis of national TB registry data for 2011 to 2021. SETTING: United States. PARTICIPANTS: U.S.-born persons stratified by race/ethnicity. MEASUREMENTS: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. RESULTS: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. LIMITATION: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. CONCLUSION: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Racial and ethnic disparities in diagnosis and treatment outcomes among US-born people diagnosed with tuberculosis, 2003-19: an analysis of national surveillance data.

BACKGROUND: Persistent racial and ethnic disparities in tuberculosis incidence exist in the USA, however, less is known about disparities along the tuberculosis continuum of care. This study aimed to describe how race and ethnicity are associated with tuberculosis diagnosis and treatment outcomes. METHODS: In this analysis of national surveillance data, we extracted data from the US National Tuberculosis Surveillance System on US-born patients with tuberculosis during 2003-19. To estimate the association between race and ethnicity and tuberculosis diagnosis (diagnosis after death, cavitation, and sputum smear positivity) and treatment outcomes (treatment for more than 12 months, treatment discontinuation, and death during treatment), we fitted log-binomial regression models adjusting for calendar year, sex, age category, and regional division. Race and ethnicity were defined based on US Census Bureau classification as White, Black, Hispanic, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and people of other ethnicities. We quantified racial and ethnic disparities as adjusted relative risks (aRRs) using non-Hispanic White people as the reference group. We also calculated the Index of Disparity as a summary measure that quantifies the dispersion in a given outcome across all racial and ethnic groups, relative to the population mean. We estimated time trends in each outcome to evaluate whether disparities were closing or widening. FINDINGS: From 2003 to 2019, there were 72 809 US-born individuals diagnosed with tuberculosis disease of whom 72 369 (35·7% women and 64·3% men) could be included in analyses. We observed an overall higher risk of any adverse outcome (defined as diagnosis after death, treatment discontinuation, or death during treatment) for non-Hispanic Black people (aRR 1·27, 95% CI 1·22-1·32), Hispanic people (1·20, 1·14-1·27), and American Indian or Alaska Native people (1·24, 1·12-1·37), relative to non-Hispanic White people. The Index of Disparity for this summary outcome remained unchanged over the study period. INTERPRETATION: This study, based on national surveillance data, indicates racial and ethnic disparaties among US-born tuberculosis patients along the tuberculosis continuum of care. Initiatives are needed to reduce diagnostic delays and improve treatment outcomes for US-born racially marginalised people in the USA. FUNDING: US Centers for Disease Control and Prevention.

Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring.

Cancer is the primary cause of death in economically developed countries and the second leading cause in developing countries. Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide. Risk factors for CRC include obesity, a diet low in fruits and vegetables, physical inactivity, and smoking. CRC has a poor prognosis, and there is a critical need for new diagnostic and prognostic biomarkers to reduce related deaths. Recently, studies have focused more on molecular testing to guide targeted treatments for CRC patients. The most crucial feature of activated immune cells is the production and release of growth factors and cytokines that modulate the inflammatory conditions in tumor tissues. The cytokine network is valuable for the prognosis and pathogenesis of colorectal cancer as they can aid in the cost-effective and non-invasive detection of cancer. A large number of interleukins (IL) released by the immune system at various stages of CRC can act as "biomarkers". They play diverse functions in colorectal cancer, and include IL-4, IL-6, IL-8, IL-11, IL-17A, IL-22, IL-23, IL-33, TNF, TGF-ß, and vascular endothelial growth factor (VEGF), which are pro-tumorigenic genes. However, there are an inadequate number of studies in this area considering its correlation with cytokine profiles that are clinically useful in diagnosing cancer. A better understanding of cytokine levels to establish diagnostic pathways entails an understanding of cytokine interactions and the regulation of their various biochemical signaling pathways in healthy individuals. This review provides a comprehensive summary of some interleukins as immunological biomarkers of CRC.

Diagnosis, Treatment, and Prevention of Tuberculosis Among People Experiencing Homelessness in the United States: Current Recommendations.

OBJECTIVE: Tuberculosis (TB) is a public health problem, especially among people experiencing homelessness (PEH). The Advisory Council for the Elimination of Tuberculosis issued recommendations in 1992 for TB prevention and control among PEH. Our goal was to provide current guidelines and information in one place to inform medical and public health providers and TB programs on TB incidence, diagnosis, and treatment among PEH. METHODS: We reviewed and synthesized diagnostic and treatment recommendations for TB disease and latent TB infection (LTBI) as of 2022 and information after 1992 on the magnitude of homelessness in the United States, the incidence of TB among PEH, the role of public health departments in TB case management among PEH, and recently published evidence. RESULTS: In 2018, there were 1.45 million estimated PEH in the United States. During the past 2 decades, the incidence of TB was >10 times higher and the prevalence of LTBI was 7 to 20 times higher among PEH than among people not experiencing homelessness. TB outbreaks were common in overnight shelters. Permanent housing for PEH and the use of rapid TB diagnostic tests, along with isolation and treatment, reduced TB exposure among PEH. The use of direct observation enhanced treatment adherence among PEH, as did involvement of social workers to help secure shelter, food, safety, and treatment for comorbidities, especially HIV and substance use disorders. Testing and treatment for LTBI prevented progression to TB disease, and shorter LTBI regimens helped improve adherence. Federal agencies and the National Health Care for the Homeless Council have helpful resources. CONCLUSION: Improvements in TB diagnosis, treatment, and prevention among PEH are possible by following existing recommendations and using client-centered approaches.

Prevalence of Tuberculosis and Mental Disorders Comorbidity: A Systematic Review and Meta-analysis.

Persons with tuberculosis (TB) also often have a mental disorder (MD). We examined TB-MD comorbidity prevalence and its impact on TB treatment outcomes as reported in studies set in the United States or in the top five countries of origin (Mexico, the Philippines, India, Vietnam, and China) for non-US-born persons with TB. We searched MEDLINE, EMBASE, OVID, PsycINFO, CINAHL, and Scopus for articles published from database inception through September 2018. Of the 9 studies analyzed, one was set in the United States. The estimated pooled prevalence of comorbid TB-MD from eight non-US studies, with 2921 participants, was 34.0% [95% confidence interval (CI) 21.1%-49.5%]. Comorbid TB-MD prevalence varied by country in the studies evaluated. Additional research might elucidate the extent of TB-MD in the United States and the top five countries of origin.

Predictive value of TNF-α, IFN-γ, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada.

BACKGROUND: We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis. METHODS: We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays. RESULTS: Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively. CONCLUSIONS: Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.

Duration of Exposure Among Close Contacts of Patients With Infectious Tuberculosis and Risk of Latent Tuberculosis Infection.

BACKGROUND: Predictors of latent tuberculosis infection (LTBI) among close contacts of persons with infectious tuberculosis (TB) are incompletely understood, particularly the number of exposure hours. METHODS: We prospectively enrolled adult patients with culture-confirmed pulmonary TB and their close contacts at 9 health departments in the United States and Canada. Patients with TB were interviewed and close contacts were interviewed and screened for TB and LTBI during contact investigations. RESULTS: LTBI was diagnosed in 1390 (46%) of 3040 contacts, including 624 (31%) of 2027 US/Canadian-born and 766 (76%) of 1013 non-US/Canadian-born contacts. In multivariable analysis, age ≥5 years, male sex, non-US/Canadian birth, smear-positive index patient, and shared bedroom with an index patient (P < .001 for each), as well as exposure to >1 index patient (P < .05), were associated with LTBI diagnosis. LTBI prevalence increased with increasing exposure duration, with an incremental prevalence increase of 8.2% per 250 exposure hours (P < .0001). For contacts with <250 exposure hours, no difference in prevalence was observed per 50 exposure hours (P = .63). CONCLUSIONS: Hours of exposure to a patient with infectious TB is an important LTBI predictor, with a possible risk threshold of 250 hours. More exposures, closer exposure proximity, and more extensive index patient disease were additional LTBI predictors.

Risk Factors for Tuberculosis and Effect of Preventive Therapy Among Close Contacts of Persons With Infectious Tuberculosis.

BACKGROUND: Close contacts of persons with pulmonary tuberculosis (TB) have high rates of TB disease. METHODS: We prospectively enrolled TB patients and their close contacts at 9 US/Canadian sites. TB patients and contacts were interviewed to identify index patient, contact, and exposure risk factors for TB. Contacts were evaluated for latent TB infection (LTBI) and TB, and the effectiveness of LTBI treatment for preventing contact TB was examined. RESULTS: Among 4490 close contacts, multivariable risk factors for TB were age ≤5 years, US/Canadian birth, human immunodeficiency virus infection, skin test induration ≥10 mm, shared bedroom with an index patient, exposure to more than 1 index patient, and index patient weight loss (P < .05 for each). Of 1406 skin test-positive contacts, TB developed in 49 (9.8%) of 446 who did not initiate treatment, 8 (1.8%) of 443 who received partial treatment, and 1 (0.2%) of 517 who completed treatment (1951, 290, and 31 cases/100 000 person-years, respectively; P < .001). TB was diagnosed in 4.2% of US/Canadian-born compared with 2.3% of foreign-born contacts (P = .002), and TB rates for US/Canadian-born and foreign-born contacts who did not initiate treatment were 3592 and 811 per 100 000 person-years, respectively (P < .001). CONCLUSIONS: Treatment for LTBI was highly effective in preventing TB among close contacts of infectious TB patients. Several index patient, contact, and exposure characteristics associated with increased risk of contact TB were identified. These findings help inform contact investigation, LTBI treatment, and other public health prevention efforts.

Changes in Tuberculosis Disparities at a Time of Decreasing Tuberculosis Incidence in the United States, 1994-2016.

OBJECTIVES: To assess national progress in reducing disparities in rates of tuberculosis (TB) disease, which disproportionately affects minorities. METHODS: We used Centers for Disease Control and Prevention (CDC) surveillance data and US Census data to calculate TB rates for 1994 through 2016 by race/ethnicity, national origin, and other TB risk factors. We assessed progress in reducing disparities with rate ratios (RRs) and indexes of disparity, defined as the average of the differences between subpopulation and all-population TB rates divided by the all-population rate. RESULTS: Although TB rates decreased for all subpopulations, RRs increased or stayed the same for all minorities compared with Whites. For racial/ethnic groups, indexes of disparity decreased from 1998 to 2008 (P < .001) but increased thereafter (P = .33). The index of disparity by national origin increased an average of 1.5% per year. CONCLUSIONS: Although TB rates have decreased, disparities have persisted and even increased for some populations. To address the problem, the CDC's Division of TB Elimination has focused on screening and treating latent TB infection, which is concentrated among minorities and is the precursor for more than 85% of TB cases in the United States.

Screening for Latent Tuberculosis Infection Among HIV-Infected Medicaid Enrollees.

OBJECTIVES: In the United States, universal screening for latent tuberculosis (TB) infection among people with HIV is recommended, but the percentage receiving screening is unknown. This study assessed screening for latent TB infection among people with HIV enrolled in Medicaid during 2006-2010. METHODS: We used nationwide fee-for-service Medicaid records to identify people with HIV, measure screening for latent TB infection, and examine associated demographic, social, and clinical factors. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We created 2 multivariate models to prevent collinearity between variables for length of HIV infection. RESULTS: Of 152 831 people with HIV, 26 239 (17.2%) were screened for latent TB infection. The factor most strongly associated with screening was TB exposure or suspected TB (OR = 3.78; 95% CI, 3.27-4.37). Significant demographic characteristics associated with screening included being African American (OR = 1.28; 95% CI, 1.24-1.32) or ≤20 years of age (OR = 1.35; 95% CI, 1.28-1.42). Significant clinical and social factors associated with screening included poor housing conditions, low body mass index, chemotherapy treatment, and use of certain substances (ORs ranged from 1.24 [95% CI, 1.20-1.27] to 1.47 [95% CI, 1.22-1.76]). The screening rate for latent TB infection was higher among people with newly diagnosed HIV infection than among those with established infection (OR = 1.37; 95% CI, 1.32-1.41) and among people with a longer established HIV infection than among those with shorter HIV infection (OR = 1.24; 95% CI, 1.23-1.26 for each additional year). CONCLUSION: Screening for latent TB infection among fee-for-service Medicaid beneficiaries with HIV was suboptimal, despite the presence of demographic, social, or clinical characteristics that should have increased the likelihood of screening. The lack of certain data in Medicaid may have resulted in an underestimation of screening.

Risk and Timing of Tuberculosis Among Close Contacts of Persons with Infectious Tuberculosis.

Background: The risk and timing of tuberculosis among recently exposed close contacts of patients with infectious tuberculosis are not well established. Methods: We prospectively enrolled patients ≥15 years of age with culture-confirmed pulmonary tuberculosis and their close contacts at 9 health departments in the United States and Canada. Close contacts were screened and cross-matched with tuberculosis registries to identify those who developed tuberculosis. Results: Tuberculosis was diagnosed in 158 of 4490 contacts (4%) of 718 index patients with tuberculosis. Of tuberculosis cases among contacts, cumulative totals of 81 (51%), 119 (75%), 128 (81%), and 145 (92%) were diagnosed by 1, 3, 6, and 12 months, respectively, after the index patients' diagnosis. Tuberculosis rates among contacts were 2644, 115, 46, 69, and 25 cases per 100000 persons, respectively, in the 5 consecutive years after the index patients' diagnosis. Of the tuberculosis cases among contacts, 121 (77%) were identified by contact investigation and 37 (23%) by tuberculosis registry cross-match. Conclusions: Close contacts to infectious patients with tuberculosis had high rates of tuberculosis, with most disease diagnosed before or within 3 months after the index patient' diagnosis. Contact investigations need to be prompt to detect tuberculosis and maximize the opportunity to identify and treat latent infection, to prevent disease.

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. METHODS: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. FINDINGS: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1-7·3), but no significant effect on mortality (aOR 0·7, 0·4-1·1) or acquired rifampicin resistance (aOR 0·1, 0·0-1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2-0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. INTERPRETATION: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. FUNDING: World Health Organization and Canadian Institutes of Health Research.

Factors Associated With Noncompletion of Latent Tuberculosis Infection Treatment: Experience From the PREVENT TB Trial in the United States and Canada.

BACKGROUND: Overall rates of noncompletion of treatment (NCT) for latent tuberculosis infection (LTBI) in the PREVENT TB trial were 18% for 3 months of directly observed once-weekly rifapentine (maximum dose, 900 mg) plus isoniazid (maximum dose, 900 mg) (3HP-DOT) and 31% for 9 months of daily self-administered isoniazid (maximum dose, 300 mg; 9H-SAT). NCT for LTBI reduces its effectiveness. The study objective was to assess factors associated with NCT for LTBI among adult participants enrolled at US and Canadian sites of the PREVENT TB trial. METHODS: This was a post hoc exploratory analysis of the randomized, open-label PREVENT TB trial. Factors were analyzed by univariate and multivariate logistic regression (with enrollment site as a random effect). RESULTS: From 6232 participants analyzed, 1406 (22.6%) did not complete LTBI treatment (317 NCT attributed to an adverse event [NCT-AE] and 1089 NCT attributed to reasons other than an adverse event [NCT-O]). The proportion of NCT-AE was similar with both regimens (3HP-DOT = 6.4% vs 9H-SAT = 5.9%; P = .23); NCT-O was higher among participants enrolled in 9H-SAT (9H-SAT = 24.5% vs 3HP-DOT = 12.7%; P = .02). Among those in the NCT-AE group, being non-Hispanic and receiving 3HP-DOT, having cirrhosis and receiving 9H-SAT, alcohol consumption among men, and use of concomitant medication were associated with NCT-AE. Among those in the NCT-O group, receiving 9H-SAT, missing ≥1 early visit, men receiving 9H-SAT, men with a history of incarceration, alcohol abuse, use ever of intravenous drugs, younger age receiving 9H-SAT, and smoking were associated with NCT-O. CONCLUSIONS: Factors associated with NCT, such as missing a clinic visit early during treatment, might help identify persons for whom tailored interventions could improve completion of LTBI treatment. CLINICAL TRIALS REGISTRATION: NCT00023452.

Tuberculosis Contact Investigations--United States, 2003-2012.

Mycobacterium tuberculosis is transmitted through the air from an infectious patient (index patient) to other persons (contacts) who share space. Exposure to M. tuberculosis can result in tuberculosis (TB) disease or latent TB infection (LTBI), which has no clinical symptoms or radiologic evidence of disease. The cycle of transmission can be ended by isolating and treating patients with TB disease, examining contacts, and treating LTBI to prevent progression to TB disease. CDC systematically collects aggregate data on contact investigations from the 50 states, the District of Columbia (DC), and Puerto Rico. Data from 2003-2012 were analyzed for trends in yields from contact investigations, in terms of numbers of contacts elicited and examined and the estimated number of TB cases averted through treatment of LTBI among contacts in 2012. During 2003-2012, the number of TB cases decreased, while the number of contacts listed per index patient with contacts elicited increased. In 2012, U.S. public health authorities reported 9,945 cases of TB disease (1) and 105,100 contacts. Among these contacts, 84,998 (80.9%) were examined; TB was diagnosed in 532 (0.6%) and LTBI in 15,411 (18.1%). Among contacts with LTBI, 10,137 (65.8%) started treatment, and 6,689 (43.4% of all contacts with LTBI) completed treatment. By investigating contacts in 2012, an estimated 128 TB cases (34% of all potential cases) over the initial 5 years were averted, but an additional 248 cases (66%) might have been averted if all potentially contagious TB patients had contacts elicited, all contacts were examined, and all infected contacts completed treatment. Enhancing contact investigation activities, particularly by ensuring completion of treatment by contacts recently infected with M. tuberculosis, is essential to achieve the goal of TB elimination.

Tuberculosis Elimination Efforts in the United States in the Era of Insurance Expansion and the Affordable Care Act.

The Patient Protection and Affordable Care Act can enhance ongoing efforts to control tuberculosis (TB) in the United States by bringing millions of currently uninsured Americans into the health-care system. However, much of the legislative and financial framework that provides essential public health services necessary for effective TB control is outside the scope of the law. We identified three key issues that will still need to be addressed after full implementation of the Affordable Care Act: (1) essential TB-related public health functions will still be needed and will remain the responsibility of federal, state, and local health departments; (2) testing and treatment for latent TB infection (LTBI) is not covered explicitly as a recommended preventive service without cost sharing or copayment; and (3) remaining uninsured populations will disproportionately include groups at high risk for TB. To improve and continue TB control efforts, it is important that all populations at risk be tested and treated for LTBI and TB; that testing and treatment services be accessible and affordable; that essential federal, state, and local public health functions be maintained; that private-sector medical/public health linkages for diagnosis and treatment be developed; and that health-care providers be trained in conducting appropriate LTBI and TB clinical care.

Tuberculosis - United States, 1993-2010.

Tuberculosis (TB) is transmitted via the airborne route by person-to-person contact. Although TB is a leading cause of death on a global scale, most cases can be cured with treatment. From 1993 to 2010, the number of TB cases reported in the United States decreased from 25,103 to 11,182. Despite the decrease, TB continues to affect many communities in the United States disproportionately and unequally, especially racial/ethnic minorities and foreign-born persons. TB remains one of many diseases and health conditions with large disparities and inequalities by income, race/ethnicity, educational attainment, and other sociodemographic characteristics.

Effect of improving the quality of radiographic interpretation on the ability to predict pulmonary tuberculosis relapse.

RATIONALE AND OBJECTIVES: Chest radiographic findings are important for diagnosis and management of tuberculosis. The reliability of these findings is therefore of interest. We sought to describe interobserver reliability of chest radiographic findings in pulmonary tuberculosis, and to understand how the reliability of these findings might affect the utility of radiographic findings in predicting tuberculosis relapse. MATERIALS AND METHODS: Three blinded readers independently reviewed chest radiographs from a randomly selected group of 10% of HIV-seronegative subjects participating in a tuberculosis treatment trial. The three readers then arrived at a fourth, consensus radiographic interpretation. RESULTS: A total of 241 films obtained from 99 patients were reviewed. Agreement among the independent readers was very good for the findings of bilateral disease (kappa = 0.71-0.86 among readers) and cavitation (kappa = 0.66-0.73). The original interpretation was reasonably sensitive and specific (compared to the consensus interpretation) for bilateral disease, but the sensitivity for cavity decreased from 81% for the 2-month film to 47% at end of treatment (P = 0.013). Substituting the consensus interpretation for the original interpretation increased the odds ratio for the association between cavitation on early chest radiograph and subsequent tuberculosis relapse from 4.97 to 8.97. CONCLUSION: Radiographic findings were reasonably reliable between independent reviewers and the original interpretations. The original investigators, who knew the patient's clinical course, were less likely to identify cavitation on the end of treatment chest radiograph. Improving the reliability of these findings could improve the utility of chest radiographs for predicting tuberculosis relapse.

Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection.

STUDY OBJECTIVE: To characterize the bidirectional interaction between twice-daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection. DESIGN: Prospective cohort study. SETTING: Three clinical research centers. PATIENTS: Seven patients with HIV-related tuberculosis. INTERVENTION: Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. MEASUREMENTS AND MAIN RESULTS: Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC(0-21)) increased 22% (geometric mean 5.01 microg.hr/ml [90% confidence interval (CI) 3.25-7.71] with nelfinavir vs 4.10 microg.hr/ml [90% CI 3.18-5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.92]). Also, the AUC(0-21) for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected. CONCLUSIONS: Coadministration of rifabutin and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly.

Factors associated with loss to follow-up in a large tuberculosis treatment trial (TBTC Study 22).

INTRODUCTION: Loss to follow-up in clinical trials compromises achievement of study goals. We evaluated factors associated with loss to follow-up after completion of treatment phase in a large tuberculosis treatment trial (TBTC/USPHS Study 22) in the U.S. and Canada. METHODS: Patients who were lost to follow-up were compared to those who reached a study end-point or successfully completed follow-up. A generalized estimating equation model was used to combine patient-specific and site-specific factors. RESULTS: Of 1075 patients enrolled, 965 (89.8%) reached a study end-point, died, or completed the 2 year post-treatment follow-up phase, and 110 (10.2%) did not. Multivariate analysis showed the following factors to be independently associated with loss to follow-up: birth outside USA/Canada (OR 2.07, 95% CI 1.25-3.40, p=0.005), history of homelessness (OR 1.94, 95% CI 1.00-3.80, p=0.05), enrollment at a health department (OR 2.71, 95% CI 1.27-5.79, p=0.010), and use of any kind of incentive (cash/cash equivalent) during treatment phase (OR 3.04, 95% CI 1.73-5.33 p=0.0001). CONCLUSIONS: Cultural or linguistic factors and lack of stable housing contribute to loss to follow-up. Attention to these factors could improve long-term retention in clinical trials. Enrollment at a health department and use of incentives during treatment phase may be markers for other factors leading to loss to follow-up.

Quality assurance in a large clinical trials consortium: the experience of the Tuberculosis Trials Consortium.

Quality assurance (QA) is essential for data accuracy and proper evaluation of study objectives in clinical trials. The Tuberculosis Trials Consortium (TBTC)-a collaboration of 28 clinical sites and the Centers for Disease Control and Prevention-has developed a comprehensive QA program that provides quantitative assessments of performance based on clearly defined standards that are communicated to data collectors through a feedback process. The Implementation and Quality Committee of the TBTC developed a Site Evaluation Report (SER) that assesses performance measures (PMs) critical to the accomplishment of study objectives. PMs are defined, quantified, and evaluated, and goals and minimum acceptable scores are specified. Sites not meeting a PM minimum must provide an explanation and develop a plan to meet the goal. Site-specific and system-wide problems can be readily identified through this process. The SER is used prospectively for all TBTC treatment trials, and a Web site has been developed to maximize the availability and usefulness of performance data. The TBTC's comprehensive QA program is an example of a successful method for ensuring high quality, evaluable data.