Dynamics of interferon-gamma release assay and cytokine profiles in blood and respiratory tract specimens from mice with tuberculosis and the effect of therapy

There are limitations on diagnostic methods to differentiate between active and latent tuberculosis (TB), and the prediction of latent progression to TB disease is yet complex. Traditionally, tuberculosis-specific host immune response was visualized using the tuberculin skin test. Nowadays, IFN-γ release assays (IGRA) provide a more specific and sensitive tool, by which exposure to Mtb could be determined. However, the merit of IGRA aids in diagnosing active TB is yet unclear. We adapted IGRA for use in mice, and quantifying bead-based flow cytometry techniques were used to assess cytokine profiles during the course of untreated infection and to investigate the value of IGRA and cytokines as biomarkers for therapy response. High variability of IGRA results during progression of active TB infection related to various phases of infection was obtained. However, a significant decrease in IGRA results and in levels of IFN-γ, IL-17, IP-10 or MIG was observed and appeared to be associated with successful therapy. This outcome does not support the value of IGRA to accurately diagnose active TB or to monitor infection progression. However, IGRA proved to be a useful biomarker to monitor therapy success. In addition, different cytokines might serve as biomarkers

Impact of GeneXpert MTB/RIF on Patients and Tuberculosis Programs in a Low-Burden Setting. A Hypothetical Trial

Rationale: Guidelines recommend routine nucleic-acid amplification testing in patients with presumed tuberculosis (TB), but these tests have not been widely adopted. GeneXpert MTB/RIF (Xpert), a novel, semiautomated TB nucleic-acid amplification test, has renewed interest in this technology, but data from low-burden countries are limited. Objectives: We sought to estimate Xpert’s potential clinical and public health impact on empiric treatment, contact investigation, and housing in patients undergoing TB evaluation. Methods: We performed a prospective, cross-sectional study with 2-month follow-up comparing Xpert with standard strategies for evaluating outpatients for active pulmonary TB at the San Francisco Department of Public Health TB Clinic between May 2010 and June 2011. We calculated the diagnostic accuracy of standard algorithms for initial empiric TB treatment, contact investigation, and housing in reference to three Mycobacterium tuberculosis sputum cultures, as compared with that of a single sputum Xpert test. We estimated the incremental diagnostic value of Xpert, and the hypothetical reductions in unnecessary treatment, contact investigation, and housing if Xpert were adopted to guide management decisions. Measurements and Main Results: A total of 156 patients underwent Xpert testing. Fifty-nine (38%) received empiric TB treatment. Thirteen (8%) had culture-positive TB. Xpert-guided management would have hypothetically decreased overtreatment by 94%, eliminating a median of 44 overtreatment days (interquartile range, 43–47) per patient and 2,169 total overtreatment days (95% confidence interval, 1,938–2,400) annually, without reducing early detection of TB patients. We projected similar benefits for contact investigation and housing. Conclusions: Xpert could greatly reduce the frequency and impact of unnecessary empiric treatment, contact investigation, and housing, providing substantial patient and programmatic benefits if used in management decisions

Limited Utility of Name-Based Tuberculosis Contact Investigations among Persons Using Illicit Drugs: Results of an Outbreak Investigation

Persons named by a patient with tuberculosis (TB) are the focus of traditional TB contact investigations. However, patients who use illicit drugs are often reluctant to name contacts. Between January 2004 and May 2005, 18 isoniazid-resistant TB cases with matching Mycobacterium tuberculosis genotypes (spoligotypes) were reported in Miami; most patients frequented crack houses and did not name potentially infected contacts. We reviewed medical records and reinterviewed patients about contacts and locations frequented to describe transmission patterns and make recommendations to control TB in this population. Observed contacts were not named but were encountered at the same crack houses as the patients. Contacts were evaluated for latent TB infection with a tuberculosis skin test (TST). All 18 patients had pulmonary TB. Twelve (67%) reported crack use and 14 (78%) any illicit drug use. Of the 187 contacts evaluated, 91 (49%) were named, 16 (8%) attended a church reported by a patient, 61 (33%) used a dialysis center reported by a patient, and 19 (10%) were observed contacts at local crack houses. Compared to named contacts, observed contacts were eight times as likely to have positive TST results (relative risk = 7.8; 95% confidence interval = 3.8–16.1). Dialysis center and church contacts had no elevated risk of a positive TST result. Testing observed contacts may provide a higher yield than traditional name-based contact investigations for tuberculosis patients who use illicit drugs or frequent venues characterized by illicit drug use