Using risk prediction models to inform personalized, cost-effective treatment recommendations.

Objective: For many medical conditions, rapid, reliable, and affordable diagnostic tests are not available, which leads clinicians to base treatment decisions on patient symptoms and history. Although prediction models can estimate disease risk, they typically do not account for the downstream health or cost consequences of acting on their predictions. We developed and evaluated methods that integrate risk prediction with decision modeling to inform personalized, cost-effective treatment recommendations.

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.

Minimal immune cell subset differences in a cohort of close contacts of tuberculosis index cases.

Understanding the perturbations in immune response across the spectrum of TB infection is still unclear. In this study, we followed a cohort of close contacts of pulmonary TB patients with serial QFT testing at 0, 3, 6, and 12 months, and stratified them into six subgroups: QFT-increasing (low/high), QFT converters (QFT- to QFT+), QFT+ stable, and QFT- individuals. Despite these distinct QFT trajectories, we observed minimal differences in immune cell frequencies, activation profiles, and T helper subset distributions among the QFT subgroups, suggesting limited immunological stratification based on QFT dynamics alone.

Classification of unsequenced Mycobacterium tuberculosis strains in a high-burden setting using a pairwise logistic regression approach.

Over the past three decades, molecular epidemiological studies have provided new opportunities to investigate the transmission dynamics of . In most studies, a sizable fraction of individuals with notified tuberculosis cannot be included, either because they do not have culture-positive disease (and thus do not have specimens available for molecular typing) or because resources for conducting sequencing are limited. A recent study introduced a regression-based approach for inferring the membership of unsequenced tuberculosis cases in transmission clusters based on host demographic and epidemiological data.

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.

Tiled Amplicon Sequencing Enables Culture-free Whole-Genome Sequencing of Pathogenic Bacteria From Clinical Specimens.

Pathogen sequencing is an important tool for disease surveillance and demonstrated its high value during the COVID-19 pandemic. Viral sequencing during the pandemic allowed us to track disease spread, quickly identify new variants, and guide the development of vaccines. Tiled amplicon sequencing, in which a panel of primers is used for multiplex amplification of fragments across an entire genome, was the cornerstone of SARS-CoV-2 sequencing.

Understanding tuberculosis transmission and progression: A prospective cohort study of index cases and close contacts in Moldova.

Objectives: This study aims to determine the progression rate, risk factors and timeline for the progression from exposure to active tuberculosis (TB) in a high-risk population. Using a prospective cohort in the Republic of Moldova, we investigated pulmonary TB disease progression among close contacts of patients with TB in a low-burden country with high rates of drug-resistant TB.

Methods: Close contacts of patients with newly diagnosed TB were recruited and monitored to evaluate for progression rates to active TB.

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.

The recent rapid expansion of multidrug resistant Ural lineage Mycobacterium tuberculosis in Moldova.

The projected trajectory of multidrug resistant tuberculosis (MDR-TB) epidemics depends on the reproductive fitness of circulating strains of MDR M. tuberculosis (Mtb). Previous efforts to characterize the fitness of MDR Mtb have found that Mtb strains of the Beijing sublineage (Lineage 2.

Identifying local foci of tuberculosis transmission in Moldova using a spatial multinomial logistic regression model.

Background: Multidrug resistant tuberculosis (MDR-TB) represents a major public health concern in the Republic of Moldova, with an estimated 31% of new and 56% of previously treated TB cases having MDR disease in 2022. A recent genomic epidemiology study of incident TB occurring in 2018 and 2019 found that 92% of MDR-TB was the result of transmission. The MDR phenotype was concentrated among two M.

Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection.

There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens.

Predicting stringent QuantiFERON-TB Gold Plus conversions in contacts of tuberculosis patients.

Objectives: To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months.

Methods: TB patients (n = 295) and the contacts (n = 1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.

Identification of differentially recognized T cell epitopes in the spectrum of infection.

Tuberculosis caused by is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different tuberculosis (TB) infection states can help design diagnostics and vaccines. We performed a proteome-wide screen of 20,610 derived peptides in 21 Active TB (ATB) patients 3-4 months post-diagnosis of pulmonary TB (mid-treatment) using an IFNγ and IL-17 Fluorospot assay.

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 Evaluation of the XDR-LFC Assay for the Molecular Detection of Isoniazid, Rifampin, Fluoroquinolone, Kanamycin, Capreomycin, and Amikacin Drug Resistance in a Prospective Cohort.

While the goal of universal drug susceptibility testing has been a key component of the WHO End TB Strategy, in practice, this remains inaccessible to many. Rapid molecular tests for tuberculosis (TB) and antituberculosis drug resistance could significantly improve access to testing. In this study, we evaluated the accuracy of the Akonni Biosystems XDR-TB (extensively drug-resistant TB) TruArray and lateral-flow-cell (XDR-LFC) assay (Akonni Biosystems, Inc.

Detection of isoniazid, fluoroquinolone, ethionamide, amikacin, kanamycin, and capreomycin resistance by the Xpert MTB/XDR assay: a cross-sectional multicentre diagnostic accuracy study.

Background: The WHO End TB Strategy requires drug susceptibility testing and treatment of all people with tuberculosis, but second-line diagnostic testing with line-probe assays needs to be done in experienced laboratories with advanced infrastructure. Fewer than half of people with drug-resistant tuberculosis receive appropriate treatment. We assessed the diagnostic accuracy of the rapid Xpert MTB/XDR automated molecular assay (Cepheid, Sunnyvale, CA, USA) to overcome these limitations.

Evolution and emergence of multidrug-resistant in Chisinau, Moldova.

The evolution and emergence of drug-resistant tuberculosis (TB) has been studied extensively in some contexts, but the ecological drivers of these two processes remain poorly understood. This study sought to describe the joint evolutionary and epidemiological histories of a novel multidrug-resistant strain recently identified in the capital city of the Republic of Moldova (MDR Ural/4.2), where genomic surveillance of drug-resistant has been limited thus far.

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.

Molecular Detection of in Oral Mucosa from Patients with Presumptive Tuberculosis.

Tuberculosis (TB) diagnosis is increasingly based on the detection of complex (MTBC) DNA in sputum using molecular diagnostic tests as the first test for diagnosis. However, sputum can be difficult to obtain in children, patients without productive cough, and the elderly and approaches testing non-sputum samples are needed. We evaluated whether TB can be detected from the oral mucosa of patients with TB.

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.