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

Interventions to improve contact tracing for tuberculosis in specific groups and in wider populations: an evidence synthesis

Background The tracing and screening of people who have had contact with an active case of tuberculosis (TB) is an important element of TB control strategies. Objectives This study aimed to carry out a review of evidence regarding TB contact tracing, with a particular emphasis on research that was applicable to TB contact tracing in specific population groups in the UK. Design An evidence synthesis of literature of any study design on TB contact tracing in developed countries was carried out. Setting Any setting. Population Individuals found to have active TB disease, and people who have come into contact with them. Interventions Contact-tracing investigations. Main outcome measures Any outcome related to TB infection, contact investigations and/or the views of staff, people with TB disease, or their contacts. Data sources Searches for research published 1995 onwards were undertaken in the following databases: MEDLINE via Ovid SP, EMBASE via Ovid SP, EconLit via Ovid SP, PsycINFO via Ovid SP, Social Policy and Practice via Ovid SP, Cumulative Index to Nursing and Allied Health Literature via EBSCOhost, Science and Social Science Citation Indices via Web of Science and The Cochrane Library via Wiley Online Library. Review methods The study comprised a review of TB contact tracing in specific population groups and a review in wider populations. A narrative synthesis was completed and a logic model was developed from the literature. Results There were 112 articles in the review: 23 related to specific populations and 89 related to wider populations. The literature was of limited quality, with much general description of investigations. We identified only two (uncontrolled) studies that could be considered evaluative. Although the limitations of the evidence should be recognised, the review suggested the following: the value of a location-based approach, working with local communities and the media, partnership working, using molecular epidemiological testing, ensuring adequate systems and addressing fear of stigma. The literature on investigations for specific populations has much concordance with that reporting findings from wider population groups. The recognised limitations of conventional investigation methods may, however, be exacerbated in specific populations. Limitations The English-language inclusion criterion may have limited the breadth of countries represented. A meta-analysis was not possible owing to the nature of the literature. Relevant studies may have been missed by our searches, which used terminology relating to contact tracing rather than to active case finding or screening. Conclusions The review identified a sizeable volume of literature relating to contact investigations. However, it is currently predominantly descriptive, with little evaluative work underpinning investigations in either specific or wider populations. Our findings are, therefore, based on limited evidence. Further research is required if robust conclusions are to be made. Future work Research should further explore the development of measures that can be used to compare the effectiveness of different contact investigations, in studies using evaluative designs

Modern contact investigation methods for enhancing tuberculosis control in Aboriginal communities

The Aboriginal communities in Canada are challenged by a disproportionate burden of TB infection and disease. Contact investigation (CI) guidelines exist but these strategies do not take into account the unique social structure of different populations. Because of the limitations of traditional CI, new approaches are under investigation and include the use of social network analysis, geographic information systems and genomics, in addition to the widespread use of genotyping to better understand TB transmission. Guidelines for the routine use of network methods and other novel methodologies for TB CI and outbreak investigation do not exist despite the gathering evidence that these approaches can positively impact TB control efforts, even in Aboriginal communities. The feasibility and efficacy of these novel approaches to CI in Aboriginal communities requires further investigation. The successful integration of these novel methodologies will require community involvement, capacity building and ongoing support at every level. The outcome will not only be the systematic collection, analysis, and interpretation of CI data in high-burden communities to assess transmission but the prioritization of contacts who are candidates for treatment of LTBI which will break the cycle of transmission. Ultimately, the measure of success will be a clear and sustained decline in TB incidence in Aboriginal communities

Assessment of 16‐year retrospective cohort study of factors associated with non‐compliance with a tuberculosis contact tracing programme at a Spanish hospital

Rationale, aims, and objective: Contact tracing and screening is an essential strategy in tuberculosis (TB) control. Our aim is to assess factors associated with the degree of compliance with the main recommendations made to contacts of TB cases as part of the contact tracing programme, and to identify factors associated with non‐compliance. Methods: We conducted a retrospective cohort study to assess the TB contact tracing programme at a Spanish hospital over the period 1998‐2013. Results: A total 2269 contacts were identified corresponding to 644 active TB index cases, and initial screening indicated that 3.2% had active TB and 41.3% had latent TB infection (LTBI). Compliance with the recommendation for primary chemoprophylaxis increased significantly over the study period, rising from 76.5% in the period 1998 to 2002 to 82.7% in the period 2010 to 2013. A similar significant increase was also observed for latent tuberculosis infection treatment (46.1% in the first period to 68.0% in the latter period). Factors that were significantly associated with non‐compliance with the recommendations were: being of foreign origin, alcoholism, being recommended latent tuberculosis infection treatment, repeating the tuberculin skin test at 3 months, a smear‐positive index case, and an index case aged under 35 years old. Conclusions: Although compliance levels have improved over the years, it remains necessary to adopt strategies that target contacts in groups identified as being at risk of non‐compliance