Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study.

Background: In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals.

Methods: In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay.

Treatment outcomes of extensively drug-resistant tuberculosis in Europe: a retrospective cohort study.

Background: In 2021, World Health Organization revised of definition of extensive drug-resistant tuberculosis. We aimed to determine treatment outcomes of individuals affected by extensively drug-resistant tuberculosis in Europe.

Methods: This observational, retrospective cohort study included patients diagnosed with extensively drug-resistant tuberculosis in the World Health Organization European Region from 2017 to 2023.

Diagnostic accuracy study of STANDARD TB-Feron FIA and STANDARD TB-Feron ELISA tests for tuberculosis infection diagnosis in Eastern European setting.

Introduction: Tuberculosis infection (TBI) is diagnosed based on a positive immune response to antigens. This study aimed to evaluate both the qualitative and quantitative performance of two novel IGRA-based tests, the STANDARD E TB-Feron ELISA (TB-Feron-ELISA) and the STANDARD F TB-Feron FIA (IFN-γ) (TB-Feron-FIA), and compare their results to those of QuantiFERON-TB Gold Plus (QuantiFERON).

Methods: At Chiril Draganiuc Phthisiopneumology Institute in the Republic of Moldova, we prospectively enrolled three cohorts of adults: healthy individuals with no known close contact with TB, patients with active tuberculosis (TB), and individuals with a history of TB.

Fluoroquinolone Resistance in Drug-Resistant Tuberculosis, Kharkiv, Ukraine, 2019-2023.

Rifampin-resistant Mycobacterium tuberculosis was identified by the World Health Organization as a pathogen of public health critical importance. During 2014-2023, an increase in fluoroquinolone resistance in rifampin-resistant M. tuberculosis from Kharkiv, Ukraine, was observed.

The molecular bacterial load assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif.

Objectives: Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods: The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Tuberculosis in adult migrants in Europe: a TBnet consensus statement.

Introduction: Global migration has increased in recent decades owing to war, conflict, persecution and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs depending on migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for managing migrants at risk of TB often rely on expert opinions, rather than clinical evidence.

Whispers in the Wind: Face Mask Sampling for Mycobacterium tuberculosis Detection in Children With Pulmonary Tuberculosis.

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M.

Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

Background: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST).

Methods And Findings: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB.

Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017-2022.

In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).

Recent advances in the treatment of tuberculosis.

Background: Tuberculosis (TB) is a global health challenge and one of the leading causes of death worldwide. In the last decade, the TB treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid, and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, and SHINE) and drug-resistant TB (STREAM, NiX-TB, ZeNix, and TB-PRACTECAL).

Limited Nosocomial Transmission of Drug-Resistant Tuberculosis, Moldova.

Applying whole-genome-sequencing, we aimed to detect transmission events of multidrug-resistant/rifampin-resistant strains of Mycobacterium tuberculosis complex at a tuberculosis hospital in Chisinau, Moldova. We recorded ward, room, and bed information for each patient and monitored in-hospital transfers over 1 year. Detailed molecular and patient surveillance revealed only 2 nosocomial transmission events.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.

Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing.

Long-term treatment outcomes in patients with multidrug-resistant tuberculosis.

Objectives: To describe long-term treatment outcomes in patients with multi-drug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and validate established outcome definitions for MDR/RR-TB treatment.

Methods: Among patients with MDR/RR-TB admitted to a German MDR/RR-TB referral centre from 1 September 2002 to 29 February 2020, we compared long-term treatment outcomes derived from individual patient follow-up with treatment outcomes defined by WHO-2013, WHO-2021 and the Tuberculosis Network European Trials Group-2016.

Results: In a total of 163 patients (mean age, 35 years; standard deviation, 13 years; 14/163 [8.

Emergence of bedaquiline resistance in a high tuberculosis burden country.

Rationale: Bedaquiline has been classified as a group A drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) by the World Health Organization; however, globally emerging resistance threatens the effectivity of novel MDR-TB treatment regimens.

Objectives: We analysed pre-existing and emerging bedaquiline resistance in bedaquiline-based MDR-TB therapies, and risk factors associated with treatment failure and death.

Methods: In a cross-sectional cohort study, we employed patient data, whole-genome sequencing (WGS) and phenotyping of complex (MTBC) isolates.

Rapid Detection of Extensively Drug-Resistant Tuberculosis in Clinical Samples Using a Novel Tabletop Platform: Protocol for a Prospective Clinical Study.

Background: The lack of accurate and efficient diagnostic devices for extensively drug-resistant tuberculosis (XDR-TB) makes it a severe threat to global public health. A prospective clinical study in an intended-use cohort was designed to evaluate the Akonni Biosystems XDR-TB TruArray and lateral flow cell (XDR-LFC) to address this gap in tuberculosis diagnostics.

Objective: This paper presents the protocol for a study that aims to document the conceptualization and design of this evaluation method for early dissemination while data collection and analysis are ongoing.

Defining Outcomes of Tuberculosis (Treatment): From the Past to the Future.

Untreated active tuberculosis (TB) has a very high long-term mortality. Treatment of TB reduces mortality dramatically and should maximize cure, preventing ongoing transmission and TB sequelae. However, predicting the risk of failure and relapse is crucial for the management of individual patients and for the evaluation of effectiveness of programs.

Impact of bedaquiline on treatment outcomes of multidrug-resistant tuberculosis in a high-burden country.

Background: Evaluation of novel anti-tuberculosis (TB) drugs for the treatment of multidrug-resistant (MDR)-TB continues to be of high interest on the TB research agenda. We assessed treatment outcomes in patients with pulmonary MDR-TB who received bedaquiline-containing treatment regimens in the Republic of Moldova, a high-burden MDR-TB country.

Method: We systematically analysed the SIMETB national electronic TB database and performed a retrospective propensity score-matched comparison of treatment outcomes in a cohort of patients with MDR-TB who started treatment during 2016-2018 with a bedaquiline-containing regimen (bedaquiline cohort) and a cohort of patients treated without bedaquiline (non-bedaquiline cohort).

Perspective for Precision Medicine for Tuberculosis.

Tuberculosis is a bacterial infectious disease that is mainly transmitted from human to human via infectious aerosols. Currently, tuberculosis is the leading cause of death by an infectious disease world-wide. In the past decade, the number of patients affected by tuberculosis has increased by ~20 percent and the emergence of drug-resistant strains of challenges the goal of elimination of tuberculosis in the near future.

A retrospective genomic analysis of drug-resistant strains of M. tuberculosis in a high-burden setting, with an emphasis on comparative diagnostics and reactivation and reinfection status.

Background: Recurrence of drug-resistant tuberculosis (DR-TB) after treatment occurs through relapse of the initial infection or reinfection by a new drug-resistant strain. Outbreaks of DR-TB in high burden regions present unique challenges in determining recurrence status for effective disease management and treatment. In the Republic of Moldova the burden of DR-TB is exceptionally high, with many cases presenting as recurrent.

Management of drug-resistant tuberculosis.

Drug-resistant tuberculosis is a major public health concern in many countries. Over the past decade, the number of patients infected with Mycobacterium tuberculosis resistant to the most effective drugs against tuberculosis (ie, rifampicin and isoniazid), which is called multidrug-resistant tuberculosis, has continued to increase. Globally, 4·6% of patients with tuberculosis have multidrug-resistant tuberculosis, but in some areas, like Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, this proportion exceeds 25%.