Increased risk of tuberculosis among foreign-born persons with diabetes in California, 2010-2012.

BACKGROUND: Diabetes increases the risk of tuberculosis. We sought to identify populations of persons with diabetes in California at further increased risk for tuberculosis to target tuberculosis infection screening and treatment efforts. METHODS: We performed a retrospective population-based analysis of adult (aged ≥18 years) tuberculosis cases reported in California during 2010-2012. Tuberculosis cases with and without diabetes were grouped into regions of birth and stratified by age category. Population estimates were calculated using 2011-2012 California Health Interview Survey data. We calculated tuberculosis disease rate and relative risk of tuberculosis among persons with diabetes stratified by birth location and age group; and the number needed to screen and, if positive, treat for tuberculosis infection to prevent one case of active tuberculosis over 5 years (NNS). RESULTS: During 2010-2012, among 6,050 adults with active tuberculosis in California, 82% were foreign-born and 24% had diabetes. The overall relative risk for tuberculosis among persons with diabetes was 3.5 (95% confidence interval, 3.3-3.7) with a rate of 21 per 100,000 persons with diabetes. The rate among foreign-born persons with diabetes (141.5/100,000) was almost 12 times greater than among nonforeign-born persons with diabetes (12.0/100,000). The NNS was 7,930 among all adults, 2,740 among adults with diabetes, 1,526 among all foreign-born adults, and 596 among foreign-born adults with diabetes. CONCLUSIONS: In California, foreign-born persons with diabetes had significantly elevated rates of active tuberculosis. Focusing tuberculosis infection screening and treatment efforts on foreign-born persons with diabetes may be a feasible and efficient way to make progress toward tuberculosis elimination in California.

Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007.

To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.

Antituberculosis drug resistance acquired during treatment: an analysis of cases reported in California, 1994-2006.

BACKGROUND: To inform efforts to prevent antituberculosis drug resistance acquired during treatment, particularly multidrug-resistant (MDR) tuberculosis, we analyzed surveillance records from the US state with the highest morbidity. METHODS: Surveillance data from the California tuberculosis registry of cases reported between 1994 and 2006 were examined retrospectively. Crude risks of acquired resistance were estimated. Multivariate logistic regression was used to estimate odds ratios of demographic, clinical, and case management characteristics associated with acquired drug resistance (ADR), and secular trends in the incidence of ADR were assessed. RESULTS: One in 688 patients acquired MDR tuberculosis, with crude risks varying greatly by initial drug susceptibility test results: 1 in 1909 if initially susceptible to isoniazid and rifampin, 1 in 113 if initially isoniazid resistant, and 1 in 23 if initially rifampicin resistant. Acquired isoniazid and rifampicin monoresistance occurred in 1 in 1018 and 1 in 1455 patients, respectively. Independent predictors of acquired MDR tuberculosis were initial isoniazid resistance (odds ratio [OR], 19.2; 95% confidence interval [CI], 8.25-44.7; P < .001), initial rifampicin resistance (OR, 35.9; 95% CI, 8.61-150; P < .001), human immunodeficiency virus (HIV) infection (OR, 5.07; 95% CI, 1.73-14.9; P = .003), and cavitary disease in the absence of directly observed therapy throughout therapy (OR, 2.65; 95% CI, 1.05-6.69; P = .04). The annual incidence of ADR declined over the study period. CONCLUSIONS: Although ADR is rare and declining in California, its costly consequences warrant improvements in treatment practices. Our findings suggest that we ensure DOT throughout the course of therapy for patients with baseline drug resistance, cavitary disease, or HIV infection.

Resident racial and ethnic composition, neighborhood-level socioeconomic status, and COVID-19 infections in California SNFs.

BACKGROUND: In California, >29,000 residents in skilled nursing facility (SNFs) were diagnosed with novel coronavirus disease 2019 (COVID-19) between March 2020 and November 2020. Prior research suggests that SNFs serving racially and ethnically minoritized residents often have fewer resources and lower quality of care. We performed a cross-sectional analysis of COVID-19 incidence among residents in California SNFs, assessing the association of SNF-level racial and ethnic compositions and facility- and neighborhood-level (census tract- and county-level) indicators of socioeconomic status (SES). METHODS: SNFs were grouped based on racial and ethnic composition using data from the Centers for Medicare and Medicaid Services; categories included SNFs with ≥88% White residents, SNFs with ≥32% Black or Latinx residents, SNFs with ≥32% Asian residents, or SNFs not serving a high proportion of any racial and ethnic composition (mixed). SNF resident-level COVID-19 infection data were obtained from the National Healthcare Safety Network from May 25, 2020 to August 16, 2020. Multilevel mixed-effects negative binomial regressions were used to estimate incidence rate ratios (IRR) for confirmed COVID-19 infections among residents. RESULTS: Among 971 SNFs included in our sample, 119 (12.3%) had ≥88% White residents; 215 (22.1%) had ≥32% Black or Latinx residents; 78 (8.0%) had ≥32% Asian residents; and 559 (57.6%) were racially and ethnically mixed. After adjusting for confounders, SNFs with ≥32% Black or Latinx residents (IRR = 2.40 [95% CI = 1.56, 3.68]) and SNFs with mixed racial and ethnic composition (IRR = 2.12 [95% CI = 1.49, 3.03]) both had higher COVID-19 incidence rates than SNFs with ≥88% White residents. COVID-19 incidence rates were also found to be higher in SNFs with low SES neighborhoods compared to those in high SES neighborhoods. CONCLUSION: Public health personnel should consider SNF- and neighborhood-level factors when identifying facilities to prioritize for COVID-19 outbreak prevention and control.

Determinants of multidrug-resistant tuberculosis clusters, California, USA, 2004-2007.

Laboratory and epidemiologic evidence suggests that pathogen-specific factors may affect multidrug-resistant (MDR) tuberculosis (TB) transmission and pathogenesis. To identify demographic and clinical characteristics of MDR TB case clustering and to estimate the effect of specific isoniazid resistance-conferring mutations and strain lineage on genotypic clustering, we conducted a population-based cohort study of all MDR TB cases reported in California from January 1, 2004, through December 31, 2007. Of 8,899 incident culture-positive cases for which drug susceptibility information was available, 141 (2%) were MDR. Of 123 (87%) strains with genotype data, 25 (20%) were aggregated in 8 clusters; 113 (92%) of all MDR TB cases and 21 (84%) of clustered MDR TB cases occurred among foreign-born patients. In multivariate analysis, the katG S315T mutation (odds ratio 11.2, 95% confidence interval 2.2-Yen; p = 0.004), but not strain lineage, was independently associated with case clustering.

Extensively drug-resistant tuberculosis in california, 1993-2006.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions. METHODS: XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993-2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting. RESULTS: Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment. CONCLUSIONS: XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.

A systematic synthesis of direct costs to treat and manage tuberculosis disease applied to California, 2015.

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.

Multidrug resistance among persons with tuberculosis in California, 1994-2003.

CONTEXT: Between 1994 and 2003, tuberculosis (TB) cases in California declined 33% (4834 to 3224). However, in 2003 California reported the largest number of cases in the nation, and over the past decade the proportion of cases with multidrug-resistant tuberculosis (MDR-TB) has not decreased. OBJECTIVE: To describe the magnitude, trends, geographic distribution, clinical characteristics, risk factors, and outcomes of MDR-TB cases reported to the California registry of Reports of Verified Cases of TB. DESIGN, SETTING, AND CASES: Analysis of 38,291 TB cases reported from all 61 local health jurisdictions in California during 1994-2003. Multidrug-resistant TB was defined as resistance to at least isoniazid and rifampin. MAIN OUTCOME MEASURES: Results of univariate and multivariable analyses of MDR-TB magnitude, trends, geographic distribution, clinical characteristics, associated factors, and outcomes. RESULTS: Of 38,291 reported TB cases, 28,712 (75%) were tested for resistance to at least isoniazid and rifampin; of these, 407 MDR-TB cases (1.4%) were reported from 38 of 61 California health jurisdictions (62%); the proportion of MDR-TB cases did not significantly change over the study period (P = .87). Cases of MDR-TB were twice as likely to have cavitary lesions compared with non-MDR-TB cases (P<.001) and were 7 times more likely to have reported previous treatment for TB (P<.001). Of MDR-TB cases with outcomes, 231 (67%) completed therapy, and those with MDR-TB were significantly less likely to complete therapy than those without MDR-TB (P<.001). Multivariate analysis identified previous TB diagnosis, positive acid-fast bacilli sputum smear results, Asian/Pacific Islander ethnicity, time in the United States less than 5 years at the time of diagnosis, and outcomes of "died" and "moved" as factors associated with MDR-TB. CONCLUSIONS: Multidrug-resistant TB, an airborne disease with limited, costly treatment options, persists in 1% to 2% of all cases despite California's control efforts. Local and global TB control efforts are needed to prevent the further development and spread of MDR-TB.

Interferon-gamma release assays for diagnosing mycobacterium tuberculosis infection in renal dialysis patients.

BACKGROUND AND OBJECTIVES: End-stage renal disease (ESRD) patients are at high risk for tuberculosis (TB). IFN-gamma release assays that assess immune responses to specific TB antigens offer potential advantages over tuberculin skin testing (TST) in screening such patients for Mycobacterium tuberculosis infection. This study sought to determine whether IFN-gamma release assay results are more closely associated with recent TB exposure than TST results. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: Prospective cohort investigation of patients at a hemodialysis center with a smear-positive case of TB. Patients without a history of TB underwent initial and repeat testing with TST, and with the IFN-gamma assays QuantiFERON-TB Gold (QFT-G) and ELISPOT test. Outcome measures included the prevalence of positive test results, identification of factors associated with positive results, and test result discordance. RESULTS: A total of 100 (47% foreign born; median age, 55 yr; age range, 18 to 83 yr) of 124 eligible patients were enrolled. Twenty-six persons had positive TST results, 21 had positive QFT-G results, and 27 had positive ELISPOT results. Patients with TB case contact were likely to have a positive QFT-G result (P = 0.02) and ELISPOT results (P = 0.04), whereas TB case contact was not associated with positive TST results (P = 0.7). Positive TST results were associated with foreign birth (P = 0.04) and having had a TST in the previous year (P = 0.04). CONCLUSIONS: Positive IFN-gamma assay results were more closely associated with recent TB exposure than were positive TST results. QFT-G and ELISPOT might offer a better method for detecting TB infection in ESRD patients.

Human exposure following Mycobacterium tuberculosis infection of multiple animal species in a Metropolitan Zoo.

From 1997 to 2000, Mycobacterium tuberculosis was diagnosed in two Asian elephants (Elephas maximus), three Rocky Mountain goats (Oreamnos americanus), and one black rhinoceros (Diceros bicornis) in the Los Angeles Zoo. DNA fingerprint patterns suggested recent transmission. An investigation found no active cases of tuberculosis in humans; however, tuberculin skin-test conversions in humans were associated with training elephants and attending an elephant necropsy.