MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities

Challenge 3: Preserving biodiversity and its functions under global change

Libros Blancos. Desafíos Científicos 2030 del CSIC, vol. 7; coordinado por Jesús Marco de Lucas y M. Victoria Moreno-Arribas; 174 p.: 17 cm. Descarga completa gratuita en el enlace: libros.csic.es/product_info.php?products_id=1483The environmental sustainability of the Earth system is at risk, and so do human welfare because of our dependency on it. Here we present challenges dealing with the understanding of how drivers of global change work, and how to minimize their effects on natural and human managed systems, with the aid of new concepts and edge-cutting technology. Their achievement should allow us to detect, understand, forecast and mitigate global change impacts related to climate change, the biodiversity crisis, polar regions, and managed ecosystems, and to improve the health of our planet in the coming decades. In the twenty-first century, biodiversity erosion has become a key scientific question at the time societal concern has increased. We propose theoretical, technological and policy-relevant challenges to preserve biodiversity and safeguard our options for future solutions to global environmental problems. We outline research areas to uncover naturally occurring processes, and to predict and mitigate the impact of global change.Peer reviewe

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report

WHO (World Health Organization) recommends countries to implement pharmacovigilance and to collect information on aDSM (active drug safety monitoring and management of adverse events-AEs). Aim of this prospective study was to evaluate the frequency and severity of AEs 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. AEs 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% males, 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 AE episodes were reported: 447 (447/504, 88.7%) were classified as minor (grade 1–2) and 57 (57/504, 11.3%) as serious (grade 3–5). The majority of the 57 serious AEs reported by 55 patients (51/57; 89.5%) ultimately resolved. Among patients reporting serious AEs some drugs held responsible were discontinued: bedaquiline in 0.35% (2/577), delamanid in 0.8% (1/121), linezolid in 1.9% (10/536) and clofazimine in 1.4% (3/213) of patients. Serious AEs were reported in 6.9% (9/131) of patients treated with amikacin, 0.4% (1/221) with ethionamide/prothionamide, 2.8% (15/536) with linezolid and 1.8% (8/498) with cycloserine/terizidone. The aDSM study provided valuable information but implementation needs scaling-up to support patient-centred care

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. Aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up