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1.
  • Abidi, S, et al. (author)
  • Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
  • 2020
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:3
  • Journal article (peer-reviewed)abstract
    • We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
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  • Borisov, S, et al. (author)
  • Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report
  • 2019
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 54:6
  • Journal article (peer-reviewed)abstract
    • The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.
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  • Collin, SM, et al. (author)
  • Effectiveness of interventions for reducing TB incidence in countries with low TB incidence: a systematic review of reviews
  • 2019
  • In: European respiratory review : an official journal of the European Respiratory Society. - : European Respiratory Society (ERS). - 1600-0617. ; 28:152
  • Journal article (peer-reviewed)abstract
    • What is the evidence base for the effectiveness of interventions to reduce tuberculosis (TB) incidence in countries which have low TB incidence?MethodsWe conducted a systematic review of interventions for TB control and prevention relevant to low TB incidence settings (<10 cases per 100 000 population). Our analysis was stratified according to “direct” or “indirect” effects on TB incidence. Review quality was assessed using AMSTAR2 criteria. We summarised the strength of review level evidence for interventions as “sufficient”, “tentative”, “insufficient” or “no” using a framework based on the consistency of evidence within and between reviews.ResultsWe found sufficient review level evidence for direct effects on TB incidence/case prevention of vaccination and treatment of latent TB infection. We also found sufficient evidence of beneficial indirect effects attributable to drug susceptibility testing and adverse indirect effects (measured as sub-optimal treatment outcomes) in relation to use of standardised first-line drug regimens for isoniazid-resistant TB and intermittent dosing regimens. We found insufficient review level evidence for direct or indirect effects of interventions in other areas, including screening, adherence, multidrug-resistant TB, and healthcare-associated infection.DiscussionOur review has shown a need for stronger evidence to support expert opinion and country experience when formulating TB control policy.
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  • Collin, SM, et al. (author)
  • Tuberculosis in the European Union and European Economic Area: a survey of national tuberculosis programmes
  • 2018
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:6
  • Journal article (peer-reviewed)abstract
    • How many European Union (EU) and European Economic Area (EEA) countries have national tuberculosis (TB) control plans/strategies, and what are the priority actions/populations and barriers to implementation?In order to answer this question, a survey of EU/EEA national TB programme leads was undertaken.The response rate was 100% (31 countries). 55% of countries reported having a national TB strategy, all of which were in implementation; five countries were preparing a strategy. 74% had a defined organisational TB control structure with central coordination and 19% had a costed programme budget; few organisational structures included patient/civil society representation. The most frequently mentioned priority TB control actions were: reaching vulnerable population groups (80%), screening for active TB in high-risk groups (63%), implementing electronic registries (60%), contact tracing and outbreak investigation (60%), and tackling multidrug-resistant TB (60%). Undocumented migrants were the most commonly (46%) identified priority population. Perceived obstacles to implementation included barriers related to care recipients (lack of TB knowledge, treatment seeking/adherence), care providers (including need for specialist training of nurses and doctors) and health system constraints (funding, communication between healthcare and social care systems).This survey has provided an insight into TB control programmes across the EU/EEA that will inform the development of a TB strategy toolkit for member states.
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  • Getahun, H, et al. (author)
  • Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries
  • 2015
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:6, s. 1563-1576
  • Journal article (peer-reviewed)abstract
    • Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone.
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  • Lonnroth, K, et al. (author)
  • Towards tuberculosis elimination: an action framework for low-incidence countries
  • 2015
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 45:4, s. 928-952
  • Journal article (peer-reviewed)abstract
    • 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.
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