Contact investigation to identify individuals with tuberculosis and latent infection with Mycobacterium tuberculosis is an important component of tuberculosis control in low tuberculosis incidence countries. This document provides evidence-based and best-practice policy recommendations for contact tracing among high-and medium-priority contacts in a variety of settings. It provides a basis for national guidelines on contact investigation and tuberculosis outbreak management, and should support countries and tuberculosis control managers in evaluating and revising national policies. A review of existing guidelines, a literature search, several meetings and consultation with experts were used to formulate and grade recommendations for action during contact investigation.Available tests to identify individuals with latent infection with M. tuberculosis are designed to identify immune response against mycobacterial antigens and have variable predictive value for the likelihood to develop active tuberculosis in different populations. Contact investigation should therefore be limited to situations with a clear likelihood of transmission or to those with a higher probability of developing active tuberculosis, for instance, young children and immunocompromised persons. A risk assessment-based approach is recommended, where the need to screen contacts is prioritised on the basis of the infectiousness of the index case, intensity of exposure and susceptibility of contacts.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB).The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting.A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed.These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

Linezolid is used to treat patients with multidrug-resistant (MDR)/extensively drugresistant (XDR)-tuberculosis (TB) cases, although clinical data on its safety, tolerability and efficacy are lacking.We performed a retrospective, nonrandomised, unblinded observational study evaluating the safety and tolerability of linezolid at 600 mg q.d. or b.i.d. in MDR/XDR-TB treatment in four European countries. Efficacy evaluation compared end-points of 45 linezolid-treated against 110 linezolid-nontreated cases.Out of 195 MDR/XDR-TB patients, 85 were treated with linezolid for a mean of 221 days. Of these, 35 (41.2%) out of 85 experienced major side-effects attributed to linezolid (anaemia, thrombocytopenia and/or polyneuropathy), requiring discontinuation in 27 (77%) cases. Most side-effects occurred after 60 days of treatment. Twice-daily administration produced more major side-effects than once-daily dosing (p50.0004), with no difference in efficacy found. Outcomes were similar in patients treated with/without linezolid (p50.8), although linezolid-treated cases had more first-line (p50.002) and second-line (p50.02) drug resistance and a higher number of previous treatment regimens (4.5 versus 2.3; p50.07).Linezolid 600 mg q.d. added to an individualised multidrug regimen may improve the chance of bacteriological conversion, providing a better chance of treatment success in only the most complicated MDR/XDR-TB cases. Its safety profile does not warrant use in cases for which there are other, safer, alternatives.

Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB.Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes.Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients.To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first-and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drugresistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.KEYWORDS: Extensively drug-resistant tuberculosis, microbiological diagnosis, outcomes, systematic review, treatment efficacy A ccording to the latest World Health Organization (WHO) estimates, approximately 9.2 million new cases of tuberculosis (TB) and 1.5 million TB-related deaths occurred in 2006. TB remains a global emergency [1]. TB treatment requires multiple antibiotics over 6 months or more to achieve cure but, for decades, no new and better drugs have been developed and licensed. In addition, drug-resistant strains of Mycobacterium tuberculosis have emerged as a serious problem. The prevalence of multidrugresistant (MDR) M. tuberculosis (defined as in vitro resistance to isoniazid and rifampicin, the two most potent first-line drugs for TB treatment) is now widely reported [2,3]. MDR strains are currently found in more than 15% of all new cases of TB in some areas of the former Soviet Union (Azerbaijan, Moldova, Ukraine and Tomsk Oblast (Russian Federation)), and in more than 10% in parts of China and other areas of the former Soviet Union (Latvia, Estonia, Kazakhstan, Uzbekistan, and Ivanovo and Mari El (both Russian Federation)) [4][5][6].Strains of M. tuberculosis resistant to second-line drugs are also emerging. Cases of extensively drug-resistant (XDR)-TB (defined as in vitro drug resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs (capreomycin, kanamycin or amikacin)) have been described around the globe [7,8] Despite the growing amount of public awareness about TB dru...

T Tu ub be er rc cu ul lo os si is s c co on nt tr ro ol l i in n E Eu ur ro op pe e a an nd d i in nt te er rn na at ti io on na al l m mi ig gr ra at ti io on nTuberculosis among the foreign population entering European countries represents an increasing and important proportion of all tuberculosis cases reported in these countries. Adequate surveillance systems allow the identification of population segments at an excess risk of tuberculosis compared to the general population. Among groups of foreigners with a risk considerably exceeding that of the general population, screening for tuberculosis and infection with M. tuberculosis yields a large number of persons in many countries who can benefit from curative and preventive interventions.The Task Force recommends that European countries: 1) have notification systems based on both mandatory laboratory and physician reports of tuberculosis cases, to allow identification of population segments at an excess incidence of tuberculosis compared to the general population; 2) consider screening of high incidence and prevalence groups among the entering foreign population for tuberculosis and infection with M. tuberculosis amenable to curative and preventive intervention; 3) utilize existing governmental and nongovernmental organizations to provide culturally and socially sensitive services to ensure proper follow-up and implementation of interventions; 4) provide comprehensive curative and preventive services to treat tuberculosis; and 5) evaluate efficiency and efficacy of screening procedures on an ongoing basis.

Interpretation of TST reactions of

The aim of the present study was to assess the cost-effectiveness of the new T-SPOT.TB assay versus the tuberculin skin test (TST) for screening contacts for latent tuberculosis (TB) infection in Switzerland.Health and economic outcomes of isoniazid treatment of 20-and 40-yr-old close contacts were compared in a Markov model over a 20-yr period following screening with TST only (at three cutoff values) and T-SPOT.TB alone or in combination with the TST.T-SPOT.TB-based treatment was cost-effective at J11,621 and J23,692 per life-year-gained (LYG) in the younger and older age group, respectively. No TST-based programmes were costeffective, except at a 15-mm cut-off in the younger group only, where the cost-effectiveness (J26,451?LYG -1 ) fell just below the willingness-to-pay threshold. Combination of the TST with T-SPOT.TB slightly reduced the total cost compared with the T-SPOT.TB alone by 4.4 and 5.0% in the younger and older groups respectively. The number of contacts treated to avoid one case of TB decreased from 50 (95% confidence interval 32-106) with the TST (10-mm cut-off) to 18 (95%CI 11-43) if T-SPOT.TB was used. Using T-SPOT.TB alone or in combination with the tuberculin skin test for screening of close contacts before latent tuberculosis infection treatment is highly cost-effective in reducing the disease burden of tuberculosis.KEYWORDS: Cost-effectiveness, interferon-c release assay, latent tuberculosis infection, latent tuberculosis infection treatment, tuberculosis S creening the contacts of patients with tuberculosis (TB) is recommended as a strategy to detect infected persons who may develop the disease at a later time. It has been demonstrated that preventive treatment, mainly with isoniazid, decreases the number of future cases of TB. This strategy is therefore recommended in countries with a low incidence rate of TB, in order to further decrease the burden of disease [1]. The effectiveness and cost-effectiveness of these programmes are strongly affected by the accuracy of identifying truly infected individuals who have a risk of developing future disease. Owing to the limited sensitivity and specificity of the tuberculin skin test (TST), it follows that the current cost-effectiveness of screening may be improved if more accurate tools are used for screening for latent tuberculosis infection (LTBI).Numerous studies screening recent contacts of infectious TB patients for LTBI using the new highly specific interferon-c release assays (IGRA) have recently been published [2][3][4][5][6][7], but no study has produced cost-effectiveness data. In two papers [8,9] the way in which IGRA can be used for cost-saving in initial screening has been discussed. However, the long-term economic consequences and healthcare outcomes of this new approach for detecting Mycobacterium tuberculosis infection were not examined in the context of subsequent treatment of LTBI in comparison with existing programmes based upon the TST.As intervention options in all therapeutic areas grow, government and third-party...

In spite of the growing awareness of emerging drug-resistant Mycobacterium tuberculosis, the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/ European Economic Area countries, with special focus on multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool.National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards.Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms.Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance.