A Cross-sectional Study of Patients With Extrapulmonary Tuberculosis and Normal Chest Radiographs - What Characteristics Were Associated With Sputum Culture Positivity?

BACKGROUND: Recognizing pulmonary involvement in tuberculosis (TB) patients is necessary to prevent TB transmission. We describe frequency and characteristics of patients with extrapulmonary TB (EPTB), normal chest radiographs, and positive sputum culture. METHODS: We analyzed data of patients ≥15 years of age with EPTB reported to the California TB registry during 2011-2017 with cultured sputum and normal chest radiographs using generalized linear modeling to estimate prevalence ratios associated with positive sputum culture. Demographic, behavioral, clinical characteristics, and testing were compared for patients with positive and negative sputum culture. RESULTS: Of 1635 patients with EPTB and normal chest radiographs, 937 (57%) had sputum culture performed, and 127 (13%) patients had positive results for Mycobacterium tuberculosis complex. Patients with positive results were more likely to: be male, experience homelessness, use substances, have HIV, and have >1 disease site. Among 85 patients with HIV co-infection, 54% had positive culture results compared with 9.5% among 852 patients without HIV co-infection. Patients with EPTB in more than 1 site were also more likely to have a positive sputum culture. CONCLUSIONS: Culturing sputum from patients with EPTB identified pulmonary cases not detected by chest radiograph, particularly among patients with HIV or >1 disease site.

Introduction and evaluation of multidrug-resistant tuberculosis supplemental surveillance in the United States.

The current tuberculosis (TB) case reporting system for the United States, the Report of Verified Case of TB (RVCT), has minimal capture of multidrug-resistant (MDR) TB treatment and adverse events. Data were abstracted in five states using the form for 13 MDR TB patients during 2012-2015. The Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems were used to evaluate attributes of the form. Unstructured interviews with pilot sites and stakeholders provided qualitative feedback. The form was acceptable, simple, stable, representative, and provided high-quality data but was not flexible or timely. For the 13 patients on whom data were collected, the median duration of treatment with an injectable medication was 216 days (IQR 203-252). Six (46%) patients reported a side effect requiring a medication change and eight (62%) had a side effect present at treatment completion. A standardized MDR TB supplemental surveillance form was well received by stakeholders whose feedback was critical to making modifications. The finalized form will be implemented nationally in 2020 and will provide MDR TB treatment and morbidity data in the United States to help ensure patients with MDR TB receive the most effective treatment regimens with the least toxic drugs.

Interferon-γ Release Assay Performance for Tuberculosis in Childhood.

BACKGROUND: Interferon-γ release assays (IGRAs) are important adjunctive tests for diagnosing tuberculosis (TB) disease in children. METHODS: We analyzed California TB registry data for patients ≤18 years with laboratory-confirmed TB disease during 2010-2015 to identify case characteristics associated with test selection and performance and measure IGRA sensitivity. RESULTS: In total, 778 cases of TB were reported; 360 were laboratory confirmed. Indeterminate IGRAs were associated with being <1 year old (prevalence rate ratio 9.23; 95% confidence interval 2.87 to 29.8) and having central nervous system disease (prevalence rate ratio 2.69; 95% confidence interval 1.06 to 6.86) on multivariable analysis. Ninety-five children had both an IGRA and tuberculin skin test (TST) performed. Among those, the sensitivity of IGRA in 5- to 18-year-olds was 96% (66 out of 69) vs 83% (57 out of 69) for TST (P = .01); IGRA sensitivity compared with TST in children ages 2 to 4 was 91% (10 out of 11) vs 91% (10 out of 11) (P > .99), and the sensitivity compared with TST in children aged <2 years was 80% (12 out of 15) vs 87% (13 out of 15) (P > .99). CONCLUSIONS: This is the largest North American analysis of IGRA use and performance among children with TB disease. In children <5 years old, IGRA sensitivity is similar to TST, but sensitivity of both tests are reduced in children <2 years old. Indeterminate results are higher in children <1 year old and in central nervous system disease. In children ≥5 years old with laboratory-confirmed TB, IGRA has greater sensitivity than TST and should be considered the preferred immunodiagnostic test..

Trends in Tuberculosis Cases Among Nursing Home Residents, California, 2000 to 2009.

OBJECTIVES: To examine trends in tuberculosis (TB) incidence and to compare demographic and clinical characteristics of nursing home (NH) residents and community-dwelling older adults. DESIGN: Prospective TB surveillance. SETTING: TB cases reported in California from 2000 to 2009. PARTICIPANTS: TB patients aged 65 and older. MEASUREMENTS: Trends in TB incidence per 100,000 population were assessed using Poisson regression. Demographic and clinical characteristics were compared using the chi-square or Wilcoxon rank-sum test. Among NH residents, risk factors for death during TB treatment were identified using logistic regression. RESULTS: From 2000 to 2009, TB incidence rates decreased significantly, from 15.9/100,000 to 8.4/100,000 (-44%, 95% confidence interval (CI) = -66% to -7%) for NH residents and from 21.2/100,000 to 15.0/100,000 (-27%, 95% CI = -29% to -24%) for community-dwelling older adults. Overall, 211 TB cases among NH residents and 6,518 cases among community-dwelling older adults were reported. NH residents were more likely than community-dwelling older adults to be older (median age 81 vs 75, P < .001), have a negative acid-fast bacilli sputum smear and positive culture (37% vs 28%, P < .001), and die while undergoing TB treatment (44% vs 14%, P < .001), and were less likely to have a positive tuberculin skin test (TST) (28% vs 44%, P < .001) and have TB care provided by a health department (20% vs 59%, P < .001). In multivariable analysis, NH residents who had a positive TST were less likely to die while undergoing TB treatment (odds ratio = 0.39, 95% CI = 0.16-0.96). CONCLUSION: TB incidence rates were lower, and reductions in incidence were greater among NH residents; community-dwelling older adults had higher TB rates and smaller reductions in incidence. Interventions that promote timely detection and treatment of TB infection and disease may be needed to reduce morbidity and mortality among NH residents.

Tuberculosis and HIV co-infection, California, USA, 1993­2008.

To understand the epidemiology of tuberculosis (TB) and HIV co-infection in California, we cross-matched incident TB cases reported to state surveillance systems during 1993­2008 with cases in the state HIV/AIDS registry. Of 57,527 TB case-patients, 3,904 (7%) had known HIV infection. TB rates for persons with HIV declined from 437 to 126 cases/100,000 persons during 1993­2008; rates were highest for Hispanics (225/100,000) and Blacks (148/100,000). Patients co-infected with TB­HIV during 2001­2008 were significantly more likely than those infected before highly active antiretroviral therapy became available to be foreign born, Hispanic, or Asian/Pacific Islander and to have pyrazinamide-monoresistant TB. Death rates decreased after highly active antiretroviral therapy became available but remained twice that for TB patients without HIV infection and higher for women. In California, HIV-associated TB has concentrated among persons from low- and middle-income countries who often acquire HIV infection in the peri-immigration period.

Developing and using performance measures based on surveillance data for program improvement in tuberculosis control.

California state and local tuberculosis (TB) programs used a systematic process to develop a set of indicators to measure and improve program performance in controlling TB. These indicators were the basis for a quality improvement process known as the TB Indicators Project. Indicators were derived from guidelines and legal mandates for clinical, case management, and surveillance standards and were assessed using established criteria. The indicators were calculated using existing surveillance data. The indicator set was field tested by local programs with high TB morbidity and subsequently revised. Collaboration with key stakeholders at all stages was crucial to developing useful and accepted indicators. Data accessibility was a critical requirement for indicator implementation. Indicators most frequently targeted for performance improvement were those perceived to be amenable to intervention. Indicators based on surveillance data can complement other public health program improvement efforts by identifying program gaps and successes and monitoring performance trends.

Matching AIDS and tuberculosis registry data to identify AIDS/tuberculosis comorbidity cases in California.

The purpose of this study was to evaluate the sensitivity and positive predictive value (PPV) of a registry data linkage procedure used in the California AIDS and Tuberculosis (TB) Registry Data Linkage Study to identify AIDS/TB comorbidity cases in California. The California AIDS registry data from 1981 to 2006 were linked to the California TB registry data from 1996 to 2006 using LinkPlus, a probabilistic record linkage program developed by the Centers for Disease Control and Prevention, and matched results were manually reviewed to determine true or false matches. We estimated the sensitivity of this procedure to range from 98.0 per cent (95% confidence interval, CI: 97.3%, 98.7%) to 98.8 per cent (95% CI: 98.1%, 99.2%), and the PPV to be 100 per cent (95% CI: 96.8%, 100.0%). Our study demonstrated the feasibility of using this linkage procedure to match AIDS and TB registry data with a very high degree of accuracy.

Rapid drug susceptibility testing with a molecular beacon assay is associated with earlier diagnosis and treatment of multidrug-resistant tuberculosis in California.

To assess the clinical impact of a molecular beacon (MB) assay that detects multidrug-resistant tuberculosis (MDR TB), we retrospectively reviewed records of 127 MDR TB patients with and without MB testing between 2004 and 2007. Use of the MB assay reduced the time to detection and treatment of MDR TB.

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.

Assessing the validity of tuberculosis surveillance data in California.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) convened a workgroup to revise the tuberculosis (TB) case report in the United States of America (U.S.). The group proposed substantial revisions. Study objectives were to systematically assess the validity and completeness of reported TB case surveillance data in California and to inform TB case report revision process. METHODS: A sample of 594 cases was retrospectively selected from the cohort of all TB cases reported during 6/1/96-5/31/97 to the State TB Registry. Cases, stratified by treatment outcome, were randomly sampled within each outcome category. Data for 53 variables were abstracted from each case's public health medical record and compared to data recorded on the TB case report. Using the medical record as the "gold standard," estimates were developed for 1) concordance, sensitivity, and positive predictive value of reported data for categorical variables; 2) the absolute mean difference between the two information source for date variables; and 3) the completeness of data on the case report and in medical record. RESULTS: At least 90% of the values for 35 (79.5%) categorical variables submitted on the TB case report form were identical to values in the medical record. Concordance between data on the case report and medical record was lower for the remaining nine (20.5%) categorical variables: status of abnormal chest x-ray (46.8%); directly observed therapy (48.6%); smear result for tissue or body fluid other than sputum (49.2%); type(s) of tissue or body fluid for smears and cultures other than sputum (76.4% and 73.9% respectively); provider type (73.4%); occupation (84.4%); sputum culture conversion (85.4%); and sputum smear result (89.6%). Case report data were more complete than data in the medical record; 2.9% versus 9.8% of data were missing/unknown, respectively. CONCLUSION: For most variables examined on the TB case report, data validity was excellent, indicating a robust surveillance system. However, lower data quality was noted for a small number of variables primarily impacting treatment adherence, including assessment and planning; advocacy; allocation and garnering of resources; and research. The study provides compelling evidence supporting the CDC workgroup's proposed revisions to the TB case report.

An ecological study of tuberculosis transmission in California.

OBJECTIVES: We evaluated the association between ecological factors and rates of tuberculosis within California, using pediatric tuberculosis as an indicator of new transmission. METHODS: Ecological variables such as racial/ethnic distribution, immigration level, education, employment, poverty, and crowding were obtained from the United States Census for each census tract in California. These data were incorporated into a negative binomial regression model with the rate of pediatric tuberculosis disease in each census tract as an outcome variable. Disease rates were obtained by geocoding reported cases. Subsections of the state (San Francisco and Los Angeles) were examined independently. RESULTS: Census tracts with lower median incomes, more racial/ethnic minorities, and more immigrants had higher rates of pediatric tuberculosis. Other frequently cited risk factors such as overcrowding and unemployment were not associated with increased disease after adjusting for other measures. Risks were comparable across regions, but subtle differences were noted. CONCLUSIONS: The techniques used in this work provide a way to examine a disease within its social context. The results confirmed that tuberculosis in California continues to be a disease of poverty and racial/ethnic minorities.