Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

Patient Involvement: A New Source of Stress in Health Care Work?

Patients have become increasingly well informed with higher expectations to be involved in decision-making processes regarding their care and treatment. However, few studies have examined the impact of patient involvement on health care providers’ partnership-building communication. The aim of this study was to measure and explore the self-reported effects of patient involvement on the work of physicians and nurses. A questionnaire survey was distributed among cardiology staff in 12 Swedish hospitals (N = 488, response rate 67%). The sample was comprised of registered nurses (RNs, n = 303), licensed practical nurses (LPNs, n = 132), and physicians (MDs, n = 53). Confirmatory factor analysis was used to examine seven questionnaire statements concerning implications of patient involvement for one’s clinical work. Regression analyses were used to examine factors associated with staff’s partnership-building communication. Analysis confirmed two distinct factors accounting for 57% of the total variance, representing both negative—“Hassles”—and positive—“Uplifts”—aspects of patient involvement. Regression analyses revealed that only positive aspects (i.e., uplifts) of patient involvement predicted staff behavior aimed at involving patients. Working with actively involved patients may be a source of stress, both negative and positive, for health care professionals. By developing work routines for involving patients in their care, health care workplaces may help health care professionals to buffer the negative effects, and enhance the positive effects, of that stress.