Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps.

En 2022, la Région européenne de l'OMS a recensé 15,1% de l'ensemble des cas de TB résistante à la rifampicine/multirésistante aux médicaments (RR/MDR-TB). La majorité de ces cas ont eu lieu dans 18 pays hautement prioritaires d'Europe orientale et d'Asie centrale, parmi lesquels de nombreux ont adhéré à une initiative dirigée par le Bureau régional de l'OMS pour l'Europe. L'objectif était de mettre en place trois schémas thérapeutiques modifiés plus courts de 9 mois, entièrement oraux, (mSTR, pour l'anglais "fully oral, 9-month modified shorter treatment regimens ¼) pour le traitement de la RR/MDR-TB dans le cadre d'une recherche opérationnelle. Ces trois schémas étaient les suivants 1) bédaquiline + linézolide + lévofloxacine + clofazimine + cyclosérine (BdqLzdLfxCfzCs) ; 2) BdqLzdLfxCfz + delamanid (Dlm) pour les enfants de plus de 6 ans et les adultes ; et 3) DlmLzdLfxCfz pour les enfants de moins de 6 ans. Le projet visait à améliorer l'efficacité des traitements, à faciliter l'application des mSTR, à promouvoir la qualité des soins et à renforcer les capacités de recherche, tout en contribuant aux connaissances mondiales sur l'utilisation des mSTR par voie orale. Entre avril 2020 et juin 2022, plus de 2 800 patients ont reçu un traitement par mSTR dans la Région Européenne de l'OMS. Cette expérience unique a encouragé la continuation de la collaboration avec les programmes nationaux de lutte contre la TB, les autorités sanitaires, les experts et les donateurs tant en Europe qu'à l'étranger. L'accent est mis sur la mise en œuvre de la recherche opérationnelle et l'amélioration de la qualité des soins dans les pays de la région où la TB est fortement prévalente. Nous avons détaillé les principes de l'initiative, ses avantages et ses inconvénients, dans l'espoir d'inciter d'autres pays à suivre cet exemple, tout en exposant les étapes à venir.

Update on IJTLD OPEN: the future is open.

The launch of IJTLD OPEN, which is fully compliant with Plan S, has extended our author base and allowed readers worldwide to access the content for free. PubMed Central (PMC) has recently approved the journal for indexing (including indexing by PubMed), which will further improve visibility and access. Because authors retain copyright they can use their articles without restriction (e.g., to post on free digital repositories), helping to further disseminate their research. All these factors help to ensure that IJTLD OPEN has maximum reach and impact. However, we recognise that fees for open access may present a barrier for authors based in low- to middle-income countries. We call on the international community to ensure funding support for open access is broadly available, with equal opportunity for researchers worldwide.

An update on the IJTLD: our latest impact factor and influence on policy-making.

We present an update on how the IJTLD is performing against targets set in our Editorial Plan for 2020-2025. In terms of impact factor, the journal is ahead of schedule, and has recently moved into quartile 1 for respiratory journals. Analysis also indicates that articles within the IJTLD are being incorporated into policy documents by international agencies and leading institutes. Data are presented to illustrate this global reach.

Commitment, partnerships and operational research: three priorities for 11 EMR countries to achieve TB elimination.

BACKGROUND: In 2022, 11 of 22 Member States of the WHO Eastern Mediterranean Region (EMR) had an estimated TB incidence of <20 cases per 100,000 population. We assessed preparedness for elimination and provided recommendations to pursue the process. METHODS: We surveyed 11 EMR national TB programme managers and collected information on eight TB elimination framework domains using a close-ended data collection tool. We compiled, consolidated and validated data, including a virtual consultation before triangulating data with other sources. RESULTS: Implementation was sufficient (≥74%) for 5 of 8 domains, highest for TB infection management, TB preventive treatment, laboratory service, drug management, drug-resistant TB and TB-HIV collaboration (89%, 83% and 78%, respectively). Countries ranked lowest for commitment (73%), operational research and infection control (63%), and partnership/collaborations (41%). Five countries reached >80% when consolidating the responses, reaching sufficient from all domains. Two reached <50%. CONCLUSION: Key identified obstacles to TB elimination in EMR were insufficient commitment/financing, sub-optimal partnerships/collaborations and operational research calling for 1) all-stakeholder-inclusive, sustainably funded TB elimination plans, 2) cost-effective tools to exchange strategic information and build operational research capacity, and 3) improved collaboration.

CONTEXTE: En 2022, 11 des 22 États membres de la Région de la Méditerranée orientale de l'OMS avaient une incidence de la TB estimée à moins de 20 cas pour 100 000 habitants. Nous avons évalué l'état de préparation à l'élimination et formulé des recommandations pour poursuivre le processus. MÉTHODES: Nous avons interrogé 11 responsables de programmes nationaux de lutte contre la TB dans la région de la Méditerranée orientale et recueilli des informations sur huit domaines du cadre d'élimination de la TB à l'aide d'un outil de collecte de données à questions fermées. Nous avons compilé, consolidé et validé les données, y compris lors d'une consultation virtuelle, avant de les trianguler avec d'autres sources. RÉSULTATS: La mise en œuvre était suffisante (≥74%) pour 5 des 8 domaines, les plus élevés étant la gestion de l'infection tuberculeuse, le traitement préventif de la TB, les services de laboratoire, la gestion des médicaments, la TB pharmacorésistante et la collaboration TB-VIH (89%, 83% et 78%, respectivement). Les pays se sont classés au dernier rang pour l'engagement (73%), la recherche opérationnelle et la lutte contre l'infection (63%) et le partenariat/la collaboration (41%). Cinq pays ont atteint >80% lors de la consolidation des réponses, atteignant un niveau suffisant dans tous les domaines. Deux pays ont atteint un taux de réponse inférieur à 50%. CONCLUSION: Les principaux obstacles à l'élimination de la TB dans les pays de l'Union européenne sont un engagement/un financement insuffisant, des partenariats/collaborations sous-optimaux et une recherche opérationnelle nécessitant 1) des plans d'élimination de la TB incluant toutes les parties prenantes et bénéficiant d'un financement durable, 2) des outils rentables permettant d'échanger des informations stratégiques et de renforcer les capacités de recherche opérationnelle, et 3) une meilleure collaboration.

Alpha-1 deficiency in severe asthma patients.

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant condition, decreases protein concentration and activity at both serum and tissue levels. Few studies investigated whether the type of SERPINA1 gene phenotype in patients with severe asthma can influence symptoms and disease control during follow-up.To assess whether the presence of a non-MM genotype of SERPINA1 in patients with severe asthma is associated with disease control, systemic and airway inflammation, lung function and comorbidities prevalence compared to severe asthma patients with a homozygous genotype (MM).Asthmatic patients belonging to Global Initiative for Asthma (GINA) step 5 were retrospectively analysed in an Italian reference asthma clinic. We collected clinical, biological and functional variables at baseline and for the three following years.Out of 73 patients enrolled, 14 (19.18%) were non-MM and 59 (80.8%) were MM. Asthmatics with non-MM genotype had lower serum AAT concentration (P = 0.004) and higher emphysema prevalence than the MM group (P = 0.003) at baseline. During follow up, only MM patients showed a significant improvement of both ACQ-6 score (P < 0.0001) and eosinophilic systemic inflammation (P < 0.0001).Our findings emphasise the importance of a screening for AAT deficiency in severe asthma, as alleles mutation may influence patient's follow-up..

TB and interstitial lung disease: a systematic review and meta-analysis.

To determine the frequency of TB among patients with interstitial lung diseases (ILDs).We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs.Twelve studies comprising 3,817 patients with ILD were found: the pooled prevalence of TB among ILD patients was 11.0% (95% CI 5.4-21.0). In the subgroup analysis, the TB rate among patients with silicosis and idiopathic pulmonary fibrosis (IPF) was respectively 35.6% (95% CI 32.6-38.8) and 4.4% (95% CI 3.6-5.3) (P = 0.00). The frequency of TB among ILD patients was higher in high TB burden countries than in low/intermediate-burden countries: 26.3%, 95% CI 17.7-37.3 vs. 4.9%, 95% CI 3.3-7.2; P = 0.00.This study shows the frequency of TB among ILD patients. The meta-analysis reveals a significantly increased prevalence of TB among ILD patients with silicosis compared to IPF, and among individuals in high TB burden countries than in those with low/intermediate burden. The study results can help physicians and policymakers make efficient decisions for prompt screening and anti-TB treatment initiation in ILD patients..