miRNA Signatures in Sera of Patients with Active Pulmonary Tuberculosis.

Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of "relevant miRNAs", we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2-90.0), and 77% (CI 64.2-85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1-92.1), and 81% (65.0-90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4-99.1), and 100% (83.9-100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the potential to discriminate between PTB and LTBI, but also among the other categories

Pregnancy in patients with tuberculosis: A TBNET cross-sectional survey

BACKGROUND: Objectives: To determine whether the incidence of tuberculosis with pregnancy is more common than would be expected from the crude birth rate; to see whether there is significant delay in the diagnosis of tuberculosis during pregnancy. METHOD: Design: A cross-sectional survey. SETTING: 13 tuberculosis clinics within different European countries and the USA. POPULATION/SAMPLE: All patients with tuberculosis seen at these clinics for a period\u2009>\u20091 year. INSTRUMENT: Questionnaire survey based on continuous data collection. MAIN OUTCOME MEASURES: number and proportion of women with tuberculosis who were pregnant; timing of diagnosis in relation to pregnancy, including those who were pregnant or delivered in the 3 months prior to the diagnosis of TB and those who developed TB within 3 months after delivery. RESULTS: Pregnancy occurred in 224 (1.5 %) of 15,217 TB patients and followed the expected rate predicted from the crude birth rate for the clinic populations. TB was diagnosed more commonly in the 3 months after delivery (n\u2009=\u2009103) than during pregnancy (n\u2009=\u200968; \u3c7 2\u2009=\u200925.1, P\u2009<\u20090.001). CONCLUSIONS: TB is diagnosed more frequently after delivery, despite variations in local TB incidence and healthcare systems

Screening for Tuberculosis in Migrants: A Survey by the Global Tuberculosis Network

Tuberculosis (TB) does not respect borders, and migration confounds global TB control and elimination. Systematic screening of immigrants from TB high burden settings and-to a lesser degree TB infection (TBI)-is recommended in most countries with a low incidence of TB. The aim of the study was to evaluate the views of a diverse group of international health professionals on TB management among migrants. Participants expressed their level of agreement using a six-point Likert scale with different statements in an online survey available in English, French, Mandarin, Spanish, Portuguese and Russian. The survey consisted of eight sections, covering TB and TBI screening and treatment in migrants. A total of 1055 respondents from 80 countries and territories participated between November 2019 and April 2020. The largest professional groups were pulmonologists (16.8%), other clinicians (30.4%), and nurses (11.8%). Participants generally supported infection control and TB surveillance established practices (administrative interventions, personal protection, etc.), while they disagreed on how to diagnose and manage both TB and TBI, particularly on which TBI regimens to use and when patients should be hospitalised. The results of this first knowledge, attitude and practice study on TB screening and treatment in migrants will inform public health policy and educational resources

Cost-effectiveness of bedaquiline in MDR and XDR tuberculosis in Italy

Objective: To evaluate the cost-effectiveness of bedaquiline plus background drug regimens (BR) for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in Italy. Methods: A Markov model was adapted to the Italian setting to estimate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR in the treatment of MDR-TB and XDR-TB over 10 years, from both the National Health Service (NHS) and societal perspective. Cost-effectiveness was evaluated in terms of life-years gained (LYG). Clinical data were sourced from trials; resource consumption for compared treatments was modelled according to advice from an expert clinicians panel. NHS tariffs for inpatient and outpatient resource consumption were retrieved from published Italian sources. Drug costs were provided by reference centres for disease treatment in Italy. A 3% annual discount was applied to both cost and effectiveness. Deterministic and probabilistic sensitivity analyses were conducted. Results: Over 10 years, BBR vs. BR alone is cost-effective, with ICERs of €16,639/LYG and €4081/LYG for the NHS and society, respectively. The sensitivity analyses confirmed the robustness of the results from both considered perspectives. Conclusion: In Italy, BBR vs. BR alone has proven to be cost-effective in the treatment of MDR-TB and XDR-TB under a range of scenarios

Management of Drug Toxicity in Mycobacterium avium Complex Pulmonary Disease: An Expert Panel Survey

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions

Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT): a prospective, open-label, randomized study

Rationale Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite ≥6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS+GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Measurements and Main Results Enrolled patients (ALIS+GBT, n=224; GBT-alone, n=112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS+GBT and 10 of 112 (8.9%) with GBT alone (OR, 4.22; 95% CI [2.08, 8.57];

Criteria for the inclusion in the study population.

<p>Criteria for the inclusion in the study population.</p

Diagnostic performances of the serum miRNA signatures in the Relevance Vector Machine (RVM).

<p>The Table reports diagnostic performances already corrected for the leave-one-out cross validation (LOOCV).</p

Receiver Operating Characteristic (ROC) based on Akaike information criterion (AIC) logistic regression for the 12-miRNA signature specific for <i>TB CHILD</i> population.

<p>AUC: area under the curve.</p