Profiling T cell activation using single-molecule fluorescence in situ hybridization and flow cytometry.

Flow cytometric characterization of Ag-specific T cells typically relies on detection of protein analytes. Shifting the analysis to detection of RNA would provide several significant advantages, which we illustrate by developing a new host immunity-based platform for detection of infections. Cytokine mRNAs synthesized in response to ex vivo stimulation with pathogen-specific Ags are detected in T cells with single-molecule fluorescence in situ hybridization followed by flow cytometry. Background from pre-existing in vivo analytes is lower for RNAs than for proteins, allowing greater sensitivity for detection of low-frequency cells. Moreover, mRNA analysis reveals kinetic differences in cytokine expression that are not apparent at the protein level but provide novel insights into gene expression programs expected to define different T cell subsets. The utility of probing immunological memory of infections is demonstrated by detecting T cells that recognize mycobacterial and viral Ags in donors exposed to the respective pathogens.

Brief guide on tuberculosis control for primary health care providers: for countries in the WHO European Region with a high and intermediate burden of tuberculosis

Tuberculosis is an increasingly serious problem in the WHO European region, particularly in the countries of eastern Europe, the Baltic States, and the Commonwealth of Independent States (CIS).Primary health care providers can play an important role in tuberculosis control through early detection of the disease, referral for treatment, and involvement in directly observed treatment. This guide has been written with the aim of developing the knowledge, awareness and skills of primary health care providers regarding tuberculosis and its prevention and control. The guide is not intended as a complete source of information on tuberculosis, but rather a summary of general principles regarding prevention, detection and treatment. The guide does not reflect specific national guidelines on TB control, and is intended to be used in conjunction with the appropriate national regulations. A reference card containing key information is included with this guide.

Rethinking the socioeconomics and geography of tuberculosis among foreign-born residents of New Jersey, 1994-1999.

OBJECTIVES: This study investigated the socioeconomic profile of foreign-born tuberculosis patients in New Jersey. METHODS: Foreign- and US-born tuberculosis patients in 1994-1999 were compared using various measures of socioeconomic status. RESULTS: Out of 4295 tuberculosis patients, 2005 (47%) were foreign-born. Foreign-born patients resided in more affluent, more educated, and less crowded areas than did US-born patients (P <.005). They were also more likely to have been employed during the 2 years before diagnosis (62% vs 41%, P <.001). Private physicians treated the majority of South Asian-born patients. CONCLUSIONS: Substantial numbers of employed foreign-born tuberculosis patients now reside in affluent New Jersey locations. Changes in tuberculosis control programs may be required when the socioeconomic status and place of residence of foreign-born populations diverge from traditional assumptions linking poverty with tuberculosis.

Evaluation of investigations conducted to detect and prevent transmission of tuberculosis.

CONTEXT: Contact investigations are routinely conducted by health departments throughout the United States for all cases of active pulmonary tuberculosis (TB) to identify secondary cases of active TB and latent TB infection and to initiate therapy as needed in these contacts. Little is known about the actual procedures followed, or the results. OBJECTIVES: To evaluate contact investigations conducted by US health departments and the outcomes of these investigations. DESIGN, SETTING, AND SUBJECTS: Review of health department records for all contacts of 349 patients with culture-positive pulmonary TB aged 15 years or older reported from 5 study areas in the United States during 1996. MAIN OUTCOME MEASURES: Number of contacts identified, fully screened, and infected per TB patient; rates of TB infection and disease among contacts of TB patients; and type and completeness of data collected during contact investigations. RESULTS: A total of 3824 contacts were identified for 349 patients with active pulmonary TB. Of the TB patients, 45 (13%) had no contacts identified. Of the contacts, 55% completed screening, 27% had an initial but no postexposure tuberculin skin test, 12% were not screened, and 6% had a history of prior TB or prior positive tuberculin skin test. Of 2095 contacts who completed screening, 68% had negative skin test results, 24% had initial positive results with no prior test result available, 7% had documented skin test conversions, and 1% had active TB at the time of investigation. Close contacts younger than 15 years (76% screened vs 65% for older age groups; P<.001) or exposed to a TB patient with a positive smear (74% screened vs 59% for those with a negative smear; P<.001) were more likely to be fully screened. Close contacts exposed to TB patients with both a positive smear and a cavitary chest radiograph were more likely to have TB infection or disease (62% vs 33% for positive smear only vs 44% for cavitary radiograph only vs 37% for neither characteristic; P<.001). A number of factors associated with TB patient infectiousness, contact susceptibility to infection, contact risk of progression to active TB, and amount of contact exposure to the TB patient were not routinely recorded in health department records. CONCLUSIONS: Improvement is needed in the complex, multistep process of contact investigations to ensure that contacts of patients with active pulmonary TB are identified and appropriately screened.