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.

Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3-5]. The disease is usually characterised by initial signs and symptoms [4-9] similar to those of related viral infections (e.g. influenza, SARS, Middle East respiratory syndrome) and tuberculosis (TB), although prognosis and complications sometimes differ. Experience with concomitant TB and COVID-19 is extremely limited. One case-control study of COVID-19 patients with interferon-γ release assay-confirmed TB infection [10] and a single case of TB with COVID-19 have been submitted to, but not yet published in, peer-reviewed journals [11]. In a recent analysis of 1217 consecutive respiratory specimens collected from COVID-19 patients (Mycobacterium tuberculosis was not tested), the authors concluded that higher rates of co-infection between SARS-CoV-2 and other respiratory pathogens can be expected [12]. The present study describes the first-ever global cohort of current or former TB patients (post-TB treatment sequelae) with COVID-19, recruited by the Global Tuberculosis Network (GTN) in eight countries and three continents. No analysis for determinants of outcome was attempted. The study is nested within the GTN project monitoring adverse drug reactions [13, 14] for which the coordinating centre has an ethics committee approval, alongside ethics clearance from participating centres according to respective national regulation [13, 14]. A specific nested database was created in collaboration with the eight countries reporting patients with TB and COVID-19; the remaining countries had not yet observed COVID-19 in their patients at the time this manuscript was written. Continuous variables, if not otherwise specified, are presented as medians with interquartile ranges. Overall, 49 consecutive patients with current or former TB and COVID-19 from 26 centres in Belgium (n=1), Brazil (Porto Alegre, Rio Grande do Sul State; n=1), France (n=12), Italy (n=17), Russia (Moscow Region; n=6), Singapore (n=1), Spain (n=10) and Switzerland (Vaud Canton; n=1) were recruited (dataset updated as of

American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis.12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Metaanalysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure).Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage f600 mg versus .600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg.The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.

No abstract

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.

If tuberculosis (TB) is to be eliminated as a global health problem in the foreseeable future, improved detection of patients, earlier diagnosis and timely identification of rifampicin resistance will be critical. New diagnostics released in recent years have improved this perspective but they require investments in laboratory infrastructure, biosafety and staff specialisation beyond the means of many resource-constrained settings where most patients live. Xpert MTB/RIF, a new assay employing automated nucleic acid amplification to detect Mycobacterium tuberculosis, as well as mutations that confer rifampicin resistance, holds the promise to largely overcome these operational challenges. In this article we position Xpert MTB/RIF in today's TB diagnostic landscape and describe its additional potential as an adjunct to surveillance and surveys, taking into account considerations of pricing and ethics. In what could serve as a model for the future formulation of new policy on diagnostics, we trace the unique process by which the World Health Organization consulted international expertise and systematically assessed published evidence and freshly emerging experience from the field ahead of its endorsement of the Xpert MTB/RIF technology in 2010, summarise subsequent research findings and guidance on who to test and how, and provide perspectives on scaling up the new technology.