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Community health centers (CHC) play a key role in latent tuberculosis infection (LTBI) testing and treatment. We performed a retrospective analysis of LTBI testing and treatment among pediatric and adult patients at a CHC with a large non-U.S.-born (USB) population during a series of quality improvement (QI) interventions from 2010 to 2019. Among 124,695 patients with primary care visits, 40% of patients were tested for tuberculosis (TB) infection and among those tested, 20% tested positive, including 39% of adults aged 50–79 years. Compared to adults aged 18–49 years, children aged 6–17 had increased odds of LTBI testing and treatment initiation [odds ratio and 95% confidence interval 3.23 (3.10, 3.36) and 1.41 (1.12, 1.79), respectively], while age ≥ 65 was associated with lower odds of both testing and treatment initiation. Over the analysis period, coinciding with unfunded QI interventions intended to reduce barriers to LTBI care, there was a significant increase in the proportion of patients receiving LTBI testing for both adults (6% to 47%, p

BACKGROUND: Hospitalization is a costly event that affects more than half of all TB patients in the United States. State-level hospitalization data are crucial in estimating the cost of TB disease and the financial impact of preventing TB.METHODS: We used California administrative hospital discharge data from 2009 to 2017 to characterize TB hospitalizations in comparison with non-neonatal, non-maternal hospitalizations. TB hospitalization was defined as a hospitalization with a TB ICD-9/10 code as the primary diagnosis. We estimated hospitalization costs in 2017 dollars from reported charges using cost-to-charge ratios.RESULTS: In comparison to persons hospitalized for other conditions, persons hospitalized for TB in 2017 were more likely to be male, of working age, and Asian/Pacific Islander. The median cost for TB hospitalizations was US$22,807 vs. US$11,568 for other hospitalizations. The median length of stay for TB hospitalizations was 12 days compared to 3 days for other hospitalizations. Medicaid was expected to pay for 50% of TB hospitalizations costing US$21,438,208.CONCLUSIONS: Societal cost estimates of TB hospitalization should be updated to reflect long hospital stays and the disproportionate burden on working age persons. This analysis enhances our understanding of the high cost of TB care and underscores the costs averted if TB cases are prevented.

Background Linezolid has been prioritized for treating multidrug-resistant tuberculosis (MDR TB), but toxicity limits its use. We report treatment outcomes for MDR TB patients in California who received standard-dose linezolid vs those who switched to low-dose. Methods We include culture-positive MDR TB cases treated with linezolid and receiving California MDR TB Service consultation during 2009–2016. Demographic, clinical, and laboratory data are analyzed using univariate analysis to compare patients who received linezolid of different dosing strategies. Analysis end points are linezolid treatment duration (measure of tolerability), treatment success (completion or cure), and adverse events (AEs). Results Sixty-nine of 194 (36%) MDR TB patients met inclusion criteria. While all patients began linezolid treatment at 600 mg daily, 39 (57%) continued at this dosage (standard-dose), and 30 (43%) switched to 300 mg daily (29%) or intermittent dosing (14%) (low dose). Patients on standard-dose linezolid were treated for 240 days, compared with 535 for those on low-dose (P < .0001). Sixty-three patients (91%) achieved treatment success, 2 (2.9%) died, 1 (1.5%) failed treatment, 1 (1.5%) stopped treatment due to side effects, and 2 (2.9%) were lost or moved. Treatment success was higher (P = .03) in the low-dose group. Sixty-two patients experienced ≥1 hematologic (71%) or neurologic (65%) AE. Those on low-dose linezolid experienced significantly (P = .03) fewer AEs per linezolid-month after switching (0.32 vs 0.10). Conclusions Patients who switched to low dose tolerated linezolid longer with better treatment outcomes and fewer recurring AEs.

Key Points Question What are the sociodemographic, clinical, and epidemiologic characteristics of persons diagnosed with tuberculosis (TB) and COVID-19 in close succession in California? Findings In this cross-sectional analysis of public health surveillance records from California residents, 91 individuals diagnosed with TB and COVID-19 more commonly had Hispanic or Latino ethnicity, diabetes, and residence in a low health equity census tract compared with those who received a TB diagnosis before the COVID-19 pandemic. Mortality rates among those diagnosed with TB and COVID-19 in close succession were higher than mortality rates among those with TB before the COVID-19 pandemic and those with COVID-19 alone. Meaning The findings of this analysis suggest that addressing long-standing health inequities and integrating prevention measures for COVID-19 and TB in California may reduce the co-occurrence of these diseases and prevent deaths., Importance Tuberculosis (TB) and COVID-19 are respiratory diseases that disproportionately occur among medically underserved populations; little is known about their epidemiologic intersection. Objective To characterize persons diagnosed with TB and COVID-19 in California. Design, Setting, and Participants This cross-sectional analysis of population-based public health surveillance data assessed the sociodemographic, clinical, and epidemiologic characteristics of California residents who were diagnosed with TB (including cases diagnosed and reported between September 3, 2019, and December 31, 2020) and COVID-19 (including confirmed cases based on positive results on polymerase chain reaction tests and probable cases based on positive results on antigen assays reported through February 2, 2021) in close succession compared with those who were diagnosed with TB before the COVID-19 pandemic (between January 1, 2017, and December 31, 2019) or diagnosed with COVID-19 alone (through February 2, 2021). This analysis included 3 402 713 California residents with COVID-19 alone, 6280 with TB before the pandemic, and 91 with confirmed or probable COVID-19 diagnosed within 120 days of a TB diagnosis (ie, TB/COVID-19). Exposures Sociodemographic characteristics, medical risk factors, factors associated with TB severity, and health equity index. Main Outcomes and Measures Frequency of reported successive TB and COVID-19 (TB/COVID-19) diagnoses within 120 days, frequency of deaths, and age-adjusted mortality rates. Results Among the 91 persons with TB/COVID-19, the median age was 58.0 years (range, 3.0-95.0 years; IQR, 41.0-73.0 years); 52 persons (57.1%) were male; 81 (89.0%) were born outside the US; and 28 (30.8%) were Asian or Pacific Islander, 4 (4.4%) were Black, 55 (60.4%) were Hispanic or Latino, 4 (4.4%) were White. The frequency of reported COVID-19 among those who received a TB diagnosis between September 3, 2019, and December 31, 2020, was 225 of 2210 persons (10.2%), which was similar to that of the general population (3 402 804 of 39 538 223 persons [8.6%]). Compared with persons with TB before the pandemic, those with TB/COVID-19 were more likely to be Hispanic or Latino (2285 of 6279 persons [36.4%; 95% CI, 35.2%-37.6%] vs 55 of 91 persons [60.4%; 95% CI, 49.6%-70.5%], respectively; P, This cross-sectional analysis uses surveillance data to examine clinical and epidemiologic characteristics of California residents diagnosed with tuberculosis and COVID-19 in close succession compared with those diagnosed with tuberculosis before the COVID-19 pandemic or COVID-19 alone.

BACKGROUND: Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups. METHODS: In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10–99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at ClinicalTrials.gov, NCT01622140. FINDINGS: Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6–1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9–2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8–1·0) and 1·3 (1·2–1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (p(trend)

Children had better treatment outcomes and lower mortality rates than adults., Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (

Background California tuberculosis (TB) prevention goals include testing more than ten million at-risk Californians and treating two million infected with tuberculosis. Adequate health insurance and robust healthcare utilization are crucial to meeting these goals, but information on these factors for populations that experience risk for TB is limited. Methods We used data from the 2014–2017 California Health Interview Survey (n = 82,758), a population-based dual-frame telephone survey to calculate survey proportions and 95% confidence intervals (CI) stratified by country of birth, focusing on persons from countries of birth with the highest number of TB cases in California. Survey proportions for recent doctor’s visit, overall health, smoking, and diabetes were age-adjusted. Results Among 18–64 year-olds, 27% (CI: 25–30) of persons born in Mexico reported being uninsured in contrast with 3% (CI: 1–5) of persons born in India. Report of recent doctor’s visit was highest among persons born in the Philippines, 84% (CI: 80–89) and lowest among Chinese-born persons, 70% (CI: 63–76). Persons born in Mexico were more likely to report community clinics as their usual source of care than persons born in China, Vietnam, or the Philippines. Poverty was highest among Mexican-born persons, 56% (CI: 54–58) and lowest among Indian-born persons, 9% (CI: 5–13). Of adults with a medical visit in a non-English language, 96% (CI: 96–97) were non-U.S.-born, but only 42% (CI: 40–44) of non-U.S.-born persons had a visit in a non-English language. Discussion Many, though not all, of the populations that experience risk for TB had health insurance and used healthcare. We found key differences in usual source of care and language use by country of birth which should be considered when planning outreach to specific providers, clinic systems, insurers and communities for TB prevention and case-finding.

Introduction Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity. Methods We created a mathematical model using all incident TB disease cases during 2013–2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015. Results We estimated that 2.7% (CI: 2.6%–2.8%) of the U.S. population, or 8.6 (CI: 8.3–8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%–1.1%) and among non-US-born persons was 13.9% (CI: 13.5%–14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45–64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%). Conclusions Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.

Objective Targeted testing and treatment of persons with latent tuberculosis infection (LTBI) is a critical component of the US tuberculosis (TB) elimination strategy. In January 2016, the California Department of Public Health issued a tool and user guide for TB risk assessment (California tool) and guidance for LTBI testing, and in September 2016, the US Preventive Services Task Force (USPSTF) issued recommendations for LTBI testing in primary care settings. We estimated the epidemiologic effect of adherence to both recommendations in California. Methods We used an individual-based Markov micro-simulation model to estimate the number of cases of TB disease expected through 2026 with baseline LTBI strategies compared with implementation of the USPSTF or California tool guidance. We estimated the risk of LTBI by age and country of origin, the probability of being in a targeted population, and the probability of presenting for primary care based on available data. We assumed 100% adherence to testing guidance but imperfect adherence to treatment. Results Implementation of USPSTF and California tool guidance would result in nearly identical numbers of tests administered and cases of TB disease prevented. Perfect adherence to either recommendation would result in approximately 7000 cases of TB disease averted (40% reduction compared with baseline) by 2026. Almost all of this decline would be driven by a reduction in the number of cases among non–US-born persons. Conclusions By focusing on the non–US-born population, adherence to LTBI testing strategies recommended by the USPSTF and the California tool could substantially reduce the burden of TB disease in California in the next decade.

BackgroundAlthough the number of patients with active tuberculosis (TB) has decreased in the last 25 years, anecdotal reports suggest that the complexity of these patients has increased. However, this complexity and its components have never been quantified or defined. We therefore aimed to describe the complexity of patients with active TB in California during 1993–2016.MethodsWe analyzed data on patient comorbidities, clinical features, and demographics from the California Department of Public Health TB Registry. All adult patients who were alive at the time of TB diagnosis in California during 1993–2016 were included in the analyses. Factors deemed by an expert panel to increase complexity (ie, increased resources or expertise requirement for successful management) were analyzed and included the following: age >75 years, HIV infection, multidrug resistance (MDR), and extrapulmonary TB disease. Second, using additional information on other comorbidities available starting in 2010, we performed exploratory factor analysis on 25 variables in order to define the dimensions of complexity.ResultsAmong the 67 512 patients analyzed, the proportion of patients with extrapulmonary disease, age >75 years, or MDR-TB each increased over the study period (P ConclusionsIn this first description of complexity in the setting of TB, we found that the complexity of patients with active TB has risen over the last 25 years in California. These findings suggest that despite the overall decline in active TB cases, effective management of more complex patients may require additional attention and resource investment.

Rationale: Mathematical modeling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a comparative analysis of tuberculosis (TB) epidemiology and potential intervention effects in California, using three previously developed epidemiologic models of TB.Objectives: To compare the influence of various modeling methods and assumptions on epidemiologic projections of domestic latent TB infection (LTBI) control interventions in California.Methods: We compared model results between 2005 and 2050 under a base-case scenario representing current TB services and alternative scenarios including: 1) sustained interruption of Mycobacterium tuberculosis (Mtb) transmission, 2) sustained resolution of LTBI and TB prior to entry of new residents, and 3) one-time targeted testing and treatment of LTBI among 25% of non-U.S.-born individuals residing in California.Measurements and Main Results: Model estimates of TB cases and deaths in California were in close agreement over the historical period but diverged for LTBI prevalence and new Mtb infections-outcomes for which definitive data are unavailable. Between 2018 and 2050, models projected average annual declines of 0.58-1.42% in TB cases, without additional interventions. A one-time LTBI testing and treatment intervention among non-U.S.-born residents was projected to produce sustained reductions in TB incidence. Models found prevalent Mtb infection and migration to be more significant drivers of future TB incidence than local transmission.Conclusions: All models projected a stagnation in the decline of TB incidence, highlighting the need for additional interventions including greater access to LTBI diagnosis and treatment for non-U.S.-born individuals. Differences in model results reflect gaps in historical data and uncertainty in the trends of key parameters, demonstrating the need for high-quality, up-to-date data on TB determinants and outcomes.

BackgroundIn 2012, the California Department of Public Health began using pyrosequencing (PSQ) to detect mutations associated with resistance to isoniazid, rifampin, quinolones and injectable drugs in Mycobacterium tuberculosis complex. We evaluated the impact of the PSQ assay on the clinical management of tuberculosis (TB) in California.MethodsTB surveillance and laboratory data for specimens submitted 1 August 2012 through 31 December 2016 were analyzed to determine time to effective treatment initiation. A survey of clinicians was used to assess how PSQ results influenced clinical decision making.ResultsOf 1957 specimens tested with PSQ, 52% were sediments and 46% were culture isolates, submitted a median of 8 and 35 days, respectively, after collection. Among 36 patients with multidrug-resistant (MDR) TB who had a sediment specimen submitted for PSQ, median time from specimen collection to MDR-TB treatment initiation was 12 days vs 51 days when PSQ was not used. Completed surveys were returned for 303 patients, 177 of whom reported a treatment change; 75 (42%) of clinicians reported PSQ as a reason for change. Twenty-one patients either had an MDR-TB risk factor and a smear-positive sputum specimen, but had PSQ performed on a culture isolate (9/36 [25%]); or did not have PSQ used for MDR-TB diagnosis (12/38 [32%]) and thus had an opportunity for earlier MDR-TB diagnosis with PSQ on sediment.ConclusionsPatients with MDR-TB initiated effective treatment 5 weeks earlier when PSQ was used compared to those without PSQ. Survey data suggest clinicians use PSQ to devise effective TB drug regimens. To maximize the benefit of PSQ, earlier submission of specimens should be prioritized.

Background Our goal was to describe the characteristics and posttreatment outcomes of pediatric patients with central nervous system (CNS) tuberculosis (TB) and to identify factors associated with poor outcome. Methods We included children aged 0 to 18 years with CNS TB reported to the California TB registry between 1993 and 2011. Demographics, clinical characteristics, severity of disease at presentation (Modified Medical Research Council stage I, II, or III [III is most severe]), treatment, and outcomes during the year after treatment completion were abstracted systematically from the medical and public health records. Patient outcomes were categorized as good or poor on the basis of disability in hearing, vision, language, ambulation, and development and other neurologic deficits. Results Among 151 pediatric CNS TB cases reported between 1993 and 2011 in California for which records were available, 92 (61%) cases included sufficient information to determine outcome. Overall, 55 (60%) children had a poor outcome. After we adjusted for age (0 to 4 years), children with stage III severity (vs I or II; prevalence rate ratio [PRR], 1.4 [95% confidence interval (CI), 1.1–1.9]), a protein concentration of >100 mg/dL on initial lumbar puncture (PRR, 1.2 [95% CI, 1.03–1.4]), or infarct on neuroimaging (PRR, 1.2 [95% CI, 1.04–1.3]) were at increased risk for a poor outcome. In multivariate analysis, an age of 0 to 4 years (vs >4 years; PRR, 1.4 [95% CI, 1.2–1.7]) and a stage II or III Modified Medical Research Council score (vs stage I; PRR, 1.2 [95% CI, 1.03–1.5]) remained significantly associated with poor outcome. Conclusions Pediatric patients with CNS TB in California are left with high rates of disabling clinical sequelae after treatment. The identification of modifiable factors is critical for improving outcomes.

Background The cost of treating and managing cases of active tuberculosis (TB) disease—from diagnosis to treatment completion—is needed by agencies working on public health budgets, resource allocation and cost-effectiveness analysis. Although components of TB costs have been published in the United States (US), no recent study has assessed overall costs for TB care and potential gaps. To systematically review the US literature for costs of treating and managing cases of active TB disease, adjust these costs to current (2015) values, and assess gaps. We quantified total direct costs—from the perspective of the health care payer—of the treatment and case management of active TB disease. Estimates were based on published figures in the US, and operational data of the California Department of Public Health. Result The average direct cost of treating and managing a TB case was $34,600 in 2015. The average cost of a multidrug-resistant TB case was $110,900. Health care spending for treating and case managing TB patients in California amounted to approximately $75.6 million for the 2133 new cases reported in 2015. Most published cost estimates were based on data from the 1990s. Conclusion TB is resource-intensive to treat and manage. Our synthesis provides inputs for budgets and economic analyses. New studies to provide original cost data are needed to better reflect current clinical and public health practices. Electronic supplementary material The online version of this article (doi:10.1186/s13104-017-2754-y) contains supplementary material, which is available to authorized users.

Rationale: To identify infected contacts of tuberculosis (TB) cases, the UK National Institute for Health and Care Excellence (NICE) recommended the addition of IFN-γ release assays (IGRA) to the tuberculin skin test (TST) in its 2006 TB guidelines. Treatment for TB infection was no longer recommended for children who screened TST-positive but IGRA-negative.

Trees can sequester air pollutants, and air pollution is associated with poor tuberculosis outcomes. However, the health impacts of urban trees on tuberculosis patients are unknown. To elucidate the effects of urban tree canopy on mortality during tuberculosis treatment, we evaluated patients diagnosed with active tuberculosis in California from 2000 through 2012, obtaining patient data from the California tuberculosis registry. Our primary outcome was all-cause mortality during tuberculosis treatment. We determined percent tree cover using 1mresolution color infrared orthoimagery categorized into land cover classes, then linked tree cover to four circular buffer zones of 50-300m radii around patient residential addresses. We used the Kaplan-Meier method to estimate survival probabilities and Cox regression models to determine mortality hazard ratios, adjusting for demographic, socioeconomic, and clinical covariates. Our cohort included 33,962 tuberculosis patients of median age 47, 59% male, 51% unemployed, and 4.9% HIV positive. Tuberculosis was microbiologically confirmed in 79%, and 1.17% were multi-drug resistant (MDR). Median tree cover was 7.9% (50m buffer). Patients were followed for 23,280 person-years with 2370 deaths during tuberculosis treatment resulting in a crude mortality rate of 1018 deaths per 10,000 person-years. Increasing tree cover quintiles were associated with decreasing mortality risk during tuberculosis treatment in all buffers, and the magnitude of association decreased incrementally with increasing buffer radius: In the 50m buffer, patients living in neighborhoods with the highest quintile tree cover experienced a 22% reduction in mortality (HR 0.78, 95%CI 0.68-0.90) compared to those living in lowest quintile tree cover; whereas for 100, 200, and 300m buffers, a 21%, 13%, and 11% mortality risk reduction was evident. In conclusion, urban tree canopy was associated with decreased mortality during tuberculosis treatment even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that trees might play a role in improving tuberculosis outcomes.

Background The California tuberculosis (TB) elimination plan calls for testing more than ten million at-risk Californians and treating two million infected with tuberculosis. Detailed knowledge about the at-risk population and the healthcare providers who serve them is crucial to further reduction of the TB burden in the state. Methods We used data from the population-based 2014-2017 California Health Interview Survey (CHIS) to examine demography, healthcare access and utilization, and language use, focusing on countries of birth with the highest number of TB cases in California. Results The six top countries of birth accounting for 62% of TB cases were Mexico, United States (U.S.), Philippines, Vietnam, China and India. CHIS data showed that poverty was highest among Mexican-born persons, 56% (CI: 54-58) and lowest among Indian-born persons, 9% (CI: 5-13). Report of recent doctor’s visit was highest among persons born in the Philippines, 84% (CI: 80-89) and lowest among Chinese-born persons, 70% (CI: 63-76). Persons born in Mexico were more likely to report community clinics as their usual source of care than persons born in China, Vietnam or the Philippines. Among 18-64 year olds, 27% (CI: 25-30) of persons born in Mexico reported being uninsured in contrast with 3% (CI: 1-5) of persons born in India. Of adults with a medical visit in a non-English language, 96% (CI: 96-97) were non-U.S.-born, but only 42% (CI: 40-44) of non-U.S.-born persons had a visit in a non-English language. Discussion Patterns of demography, healthcare utilization and language use were notably different by country of birth. These differences should be considered when planning outreach to specific providers, clinic systems, insurers and communities for TB prevention and case-finding.

The incidence of tuberculosis (TB) in the United States has stabilized, and additional interventions are needed to make progress toward TB elimination. However, the impact of such interventions depends on local demography and the heterogeneity of populations at risk. Using state-level individual-based TB transmission models calibrated to California, Florida, New York, and Texas, we modeled 2 TB interventions: 1) increased targeted testing and treatment (TTT) of high-risk populations, including people who are non–US-born, diabetic, human immunodeficiency virus (HIV)-positive, homeless, or incarcerated; and 2) enhanced contact investigation (ECI) for contacts of TB patients, including higher completion of preventive therapy. For each intervention, we projected reductions in active TB incidence over 10 years (2016–2026) and numbers needed to screen and treat in order to avert 1 case. We estimated that TTT delivered to half of the non–US-born adult population could lower TB incidence by 19.8%–26.7% over a 10-year period. TTT delivered to smaller populations with higher TB risk (e.g., HIV-positive persons, homeless persons) and ECI were generally more efficient but had less overall impact on incidence. TTT targeted to smaller, highest-risk populations and ECI can be highly efficient; however, major reductions in incidence will only be achieved by also targeting larger, moderate-risk populations. Ultimately, to eliminate TB in the United States, a combination of these approaches will be necessary.

Since 2007, immigration applicants 2-14 years old with a tuberculin skin test (TST) ≥10 mm and an otherwise negative evaluation for tuberculosis (TB) are assigned a classification for TB infection and instructed to seek domestic evaluation upon arrival in the US in accordance with Centers for Disease Control and Prevention instructions. We examined the characteristics and outcome of domestic evaluation of immigrant children who arrived in California with a positive TST on preimmigration examination to inform the preimmigration TB screening process.Retrospective analysis of the characteristics and results of domestic evaluation of immigrants 2-14 years old who arrived in California with a classification for TB infection during October 1, 2008-September 30, 2013 was performed. TB disease was determined by matching preimmigration records with the California TB registry.Among a total of 12,544 immigrant children included, 7786 (62%) were evaluated for TB postentry. Of these, 5243 (67%) were tested with TST or interferon gamma release assay (IGRA), and 2371 (45%) had a positive test. Of those tested with IGRA (n = 4035), 914 (23%) were positive. The proportion with positive IGRA increased significantly with age (years): 2-4 (11%), 5-9 (19%), 10-14 (28%), P0.0001; was lowest among arrivers from China (6%) and highest among arrivers from Mexico (48%). Nine children (0.07%) had TB disease within 5 years after arrival.The majority of immigrant children with a positive preimmigration TST tested negative for TB infection on domestic evaluation using TST or IGRA. Inclusion of IGRA in preimmigration TB screening is likely to reduce subsequent testing, treatment and cost of evaluations among immigrant children to the US.

Item does not contain fulltext BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Background An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. Methods and findings To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged, In a systematic review and meta-analysis conducted to inform World Health Organization guidelines, Elizabeth Harausz and colleagues investigate different treatment regimens and outcomes for children with multidrug-resistant tuberculosis., Author summary Why was this study done? Treatment for multidrug-resistant tuberculosis (MDR TB) affects 32,000 children per year, requires longer treatment with much more toxic medications than drug-susceptible tuberculosis. Unfortunately, little is know about the optimal treatment for children with MDR TB. This study reviewed treatment and outcome data from children around the world in order to better understand the management of MDR-TB in children. This study also sought to understand the risk factors for poor treatment outcomes in children with MDR-TB. This study informed the World Health Organization guidelines on treatment of MDR-TB in children. What did the researchers do and find? We performed a systematic review and individual patient data meta-analysis on clinical characteristics and treatment outcomes on 975 children from across 18 countries. Children were analyzed in two separate groups, those with bacteriologically confirmed MDR-TB and those who were clinically diagnosed with MDR-TB. We found that, in general, children do well when treated with the second-line MDR-TB medications (78% overall had successful treatment outcomes), despite the fact that there was a high burden of severe disease. Malnutrition and not being treated for HIV (if the child was HIV-positive) during TB treatment significantly increased the risk of poor outcomes. Second-line injectable agents and high-dose isoniazid were associated with treatment success. However, a high proportion of children with non-severe disease who received no second-line injectable agents still did well; therefore, children with non-severe disease may be able to be spared from these toxic medications. What do these findings mean? Consideration should be given to using high-dose isoniazid in treatment regimens, and if children have non-severe disease, the possibility of excluding second-line injectable agents from the treatment regimen should be considered. HIV treatment should be started as soon as is possible, and malnutrition should be aggressively treated.

SETTING Tuberculosis (TB) cases in California, USA, occur predominantly among foreign-born persons, many of whom have abnormal chest radiographs (CXRs) on overseas medical examination. These persons are recommended for follow-up TB evaluation upon arrival in the United States. OBJECTIVE To estimate the increased TB risk associated with abnormal vs. normal domestic CXRs among individuals arriving with abnormal overseas CXRs. DESIGN Cox regression analyses of 35 633 foreign-born persons aged 15 years who arrived in California during 1999-2012 with abnormal overseas CXRs and were free of imported active TB. Domestic CXRs were conducted during post-arrival evaluation. Subsequent cases through 2014 were identified from California's TB registry. RESULTS A total of 121 (0.3%) arrivers developed TB disease. Progression rates were respectively 63.6 (95%CI 50.8-76.4) and 25.4 (95% CI 15.7-35.2) cases/100 000 person-years among persons with abnormal and normal domestic CXRs. Relative to arrivers with normal domestic CXRs, those with abnormal domestic CXRs had an elevated disease risk during the first 4 years after immigration; this increased risk was greatest during the first year (hazard ratio 2.9, 95%CI 1.8-4.8). CONCLUSION Among arrivers with abnormal overseas CXRs, those with abnormal CXRs upon domestic evaluation have an elevated disease risk and represent an important target group for preventive treatment.

Tuberculosis (TB) remains an important cause of hospitalization and mortality in the United States. Prevention of TB transmission in acute care facilities relies on prompt identification and implementation of airborne isolation, rapid diagnosis, and treatment of presumptive pulmonary TB patients. In areas with low TB burden, this strategy may result in inefficient utilization of airborne infection isolation rooms (AIIRs). We reviewed TB epidemiology and diagnostic approaches to inform optimal TB detection in low-burden settings. Published clinical prediction rules for individual studies have a sensitivity ranging from 81% to 100% and specificity ranging from 14% to 63% for detection of culture-positive pulmonary TB patients admitted to acute care facilities. Nucleic acid amplification tests (NAATs) have a specificity of >98%, and the sensitivity of NAATs varies by acid-fast bacilli sputum smear status (positive smear, ≥95%; negative smear, 50%–70%). We propose an infection prevention strategy using a clinical prediction rule to identify patients who warrant diagnostic evaluation for TB in an AIIR with an NAAT. Future studies are needed to evaluate whether use of clinical prediction rules and NAATs results in optimized utilization of AIIRs and improved detection and treatment of presumptive pulmonary TB patients.Infect Control Hosp Epidemiol 2015;36(10):1215–1225

Disease was associated with the Hispanic binational population and immunosuppressive conditions, including diabetes., We conducted a retrospective review of California tuberculosis (TB) registry and genotyping data to evaluate trends, analyze epidemiologic differences between adult and child case-patients with Mycobacterium bovis disease, and identify risk factors for M. bovis disease. The percentage of TB cases attributable to M. bovis increased from 3.4% (80/2,384) in 2003 to 5.4% (98/1,808) in 2011 (p = 0.002). All (6/6) child case-patients with M. bovis disease during 2010–2011 had >1 parent/guardian who was born in Mexico, compared with 38% (22/58) of child case-patients with M. tuberculosis disease (p = 0.005). Multivariate analysis of TB case-patients showed Hispanic ethnicity, extrapulmonary disease, diabetes, and immunosuppressive conditions, excluding HIV co-infection, were independently associated with M. bovis disease. Prevention efforts should focus on Hispanic binational families and adults with immunosuppressive conditions. Collection of additional risk factors in the national TB surveillance system and expansion of whole-genome sequencing should be considered.

Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes.