This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected withMycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected withM. tuberculosis, thein vivotuberculin skin test and theex vivointerferon-γ release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with,M. tuberculosis. The proportion of individuals who truly remain infected withM. tuberculosisafter tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding onM. tuberculosislatency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection.In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TBassays with the tuberculin skin test (TST) for the diagnosis of latentMycobacterium tuberculosisinfection (LTBI).The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette–Guérin (BCG) vaccinees were evaluated.Specificity of IGRAs varied 98–100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TBand 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19–24 months varied 8–15%, exceeding those reported for the TST (2–3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3–25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases.IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion ofM. tuberculosisinfection with higher reliability.

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB).Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette–Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection withMycobacterium tuberculosis.Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistentM. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB.This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.

The prevalence of Mycobacterium tuberculosis (MTB) has increased worldwide, in part due to the HIV epidemic. Epidemiology data have demonstrated that HIV-infected individuals are more susceptible to MTB disease, which may lead to an acceleration in the progression of HIV disease. The purpose of this study was to determine whether MTB modulates HIV infection in vivo and to delineate the mechanisms involved by using in vitro model systems. Plasma viral load was measured in HIV-infected individuals before, during, and after the development of MTB disease; a 5- to 160-fold increase in viral replication was observed during the acute phase of MTB disease. In order to evaluate the mechanisms involved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in CD8+ T cell-depleted lymphocytes from HIV-infected individuals with a history of purified protein derivative (PPD) positivity but not in those who were PPD negative; this induction of HIV replication correlated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from healthy donors with a history of PPD positivity, but not in PBMC from PPD-negative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of responding T cells.