Human migrations, driven by economic hardship, conflict, and climate change, complicate the global fight against tuberculosis (TB). New strategies are needed to improve the screening of migrants for active TB disease. Current sputum-based testing methods are logistically challenging in many settings. Alternative sampling with tongue swabs is designed to be easier than sputum collection and exhibits acceptable accuracy. This study characterized the acceptability of supervised self-swabbing (SSS) for TB screening in migrant settings in Northern Italy.Migrants arriving through the Central Mediterranean route to Italy were purposely sampled to participate in in-depth interviews (IDIs), which were conducted with the support of a cultural mediator. Data was analyzed using a rapid qualitative analysis approach. The Capability, Opportunity, Motivation-Behavior (COM-B) model guided the systematic assessment of potential barriers and facilitators to SSS. Between November 2023 and June 2024, we conducted 24 IDIs with migrant men and women. Most participants preferred SSS over sputum production and found it relatively easy. Reasons for preferring SSS included its simplicity, privacy, and aversion to sputum collection. Discomfort during swabbing was rare. However, a few participants preferred sputum collection and cited oral hygiene-related complications. Participants highlighted language barriers, trust deficits with the healthcare system, and limited health literacy on infectious diseases, including TB, as factors that could limit the uptake of SSS. Participants also reported that their willingness to participate in TB screening may be driven by a need to comply with immigration rules. SSS is a promising and acceptable method for collecting samples for TB screening. To strengthen TB mitigation strategies in this population, future efforts should focus on developing culturally and linguistically tailored educational materials that address the specific concerns and informational needs of migrants.
Tuberculosis (TB) diagnosis and management in special populations remain challenging. Data about TB and transgender individuals is scarce, and strategies aimed at reducing the TB burden in this at-risk group are needed. We conducted an observational monocentric study from a national reference center for TB, including transgender individuals with active TB in a low-TB burden country (Italy), over 34 years (1990-2023). Sixty-six transgender males and two transgender females (median age 30 years, interquartile range 26-38 years, 65 migrants) were included. Most patients (38/66, 57.6%) lived in poor social conditions. 65.2% (43/66) of patients were people living with HIV. Multidrug- and rifampicin-resistant tuberculosis and isoniazid-resistant TB were diagnosed in five (7.6%) and three (4.5%) patients, respectively. The overall treatment success rate was 72.7% (48/66 patients), with differences observed according to social conditions. Our study highlights the need for a tailored approach to increase treatment success in this at-risk population.
Introduction Nontuberculous mycobacteria (NTM) are opportunistic pathogens primarily found in soil and water. Previous studies have linked higher population density and tropical/subtropical climates with increased NTM pulmonary disease (NTM-PD). However, the effects of meteorological parameters and population density on NTM incidence in European countries remain unclear. Aim This study aimed to assess whether climate conditions (temperature, humidity, wind speed, precipitation) and urbanization influence the occurrence of NTM-PD. Methods We conducted a case-control study evaluating meteorological conditions (in the 12 months before the first NTM isolate) and urbanization in the municipalities of residence of 1061 adults with NTM-PD enrolled in an Italian multicenter observational study (2017–2023), compared with a random sample of 10 000 adults from the Italian population. Results The mean age of patients was 63.1 years, and 67.2% were female. Less densely populated areas were at lower risk for NTM-PD, even after adjusting for age, sex and meteorological parameters in a multivariable mixed-effects logistic regression model (OR95%CI: 0.66, 0.56–0.78 and 0.68, 0.52–0.89 for semi-urban and rural areas, respectively, versus urban areas). Hotter climates were found to be at higher risk for NTM infection (OR95%CI 1.21 [1.10–1.33] for each °C increase in mean annual temperature). More ventilated climates with higher precipitation were at lower risk for NTM infection (OR95%CI 0.90 [0.86–0.95] for each km·h −1 increase in mean annual wind speed, 0.99 [0.99–0.99] for each 10 mm increase in mean annual precipitation). Conclusions Climate change, particularly global warming and urbanization, may increase NTM infections in regions with Mediterranean and continental climates.
A 24-year-old Ukrainian man with post-natal developmental disability was treated for presumptive facial cutaneous TB in 2018 in his home country. After moving to Italy, his nostril lesion recurred in 2021, expanding to the upper lip, but he was lost to follow-up before a diagnosis was made. In 2023, when symptoms worsened, a biopsy was performed showing chronic inflammation and negative microbiological molecular tests and culture. By 2024, the lesion spread to the eyelids with worsening ulcerations. After surgical resection, histology revealed a vegetative, haemorrhagic mucosa with necrotic granulomatous inflammation and rifampin-susceptible Mycobacterium tuberculosis (Mtb) was detected at molecular testing. Diagnosis of recurrent primary cutaneous TB without pulmonary involvement was made and treatment for drug susceptible TB was initiated, leading to complete remission of the facial lesions. Primary cutaneous TB without pulmonary involvement is rare, presenting as nodules, plaques, papules, or ulcers. Diagnosis requires systemic evaluation, imaging, infection screening and expert consultation. Cutaneous TB (CTB) is uncommon in Ukraine and accounts for less than 2% of extrapulmonary TB cases with frequent association with immunosuppression and delayed presentation. Although infrequent, CTB mirrors the wider TB scenario, that is also characterized by MDR-TB in 27% of new and 45% of retreatment cases, and XDR-TB in 13% of MDR-TB cases. In individuals coming from TB endemic areas with strong clinical suspicion, empirical TB diagnosis should always be considered despite negative microbiology to enable timely treatment and prevent progression. A multidisciplinary approach is essential for accurate diagnosis and optimal management.
Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), remains a major global health challenge. Whole genome sequencing (WGS) offers an invaluable tool for understanding the genetic diversity and drug resistance profiles of MTBC. This study provides a comprehensive WGS dataset of 2,520 MTBC isolates collected from four Italian regions—Lombardy, Piedmont, Emilia-Romagna, and Lazio—between 2017 and 2020. The dataset includes genomic data along with associated metadata, such as geographic location and drug susceptibility profiles, providing a robust resource for studying TB epidemiology and transmission dynamics. This collection represents the largest publicly available MTBC WGS dataset from Italy and has been validated to ensure accuracy and completeness. By making this dataset accessible, we aim to support collaborative research, facilitate the exploration of MTBC evolution and drug resistance, and enhance TB surveillance efforts.
ARISE was a global clinical trial designed to generate evidence demonstrating the utility of the patient-reported outcome instruments Quality of Life–Bronchiectasis (QOL-B) [Respiratory Domain (RD) only] and Patient-Reported Outcomes Measurement Information System Short Form v1.0-Fatigue 7a (PROMIS F SF-7a) in patients with newly diagnosed or recurrent Mycobacterium avium complex lung disease (MACLD). Here, we describe trial conduct, patient characteristics, and patient-reported symptoms at baseline among patients enrolled in ARISE. Adult patients with newly diagnosed or recurrent non-cavitary MACLD who had not initiated antibiotic treatment for their current MAC infection were enrolled; data including comorbidities and prior MACLD history were collected during screening. Symptom burden was assessed using QOL-B, PROMIS F SF-7a, and Functional Assessment of Chronic Illness Therapy (FACIT) questionnaires. Of 99 patients from 12 countries enrolled in ARISE, the median age was 69.0 years; most were white (80.8 People with a disease called Mycobacterium avium complex lung disease (MACLD) experience many symptoms, including cough, fatigue, and shortness of breath, which can impact their quality of life. It is not clear what symptoms people with new or repeating MACLD may have before they start antibiotic treatment for their disease. This publication describes the design of a study called ARISE, characteristics of people with MACLD who participated, and the symptoms they reported when they started the study. Overall, 99 people with a first, second, or third diagnosis of MACLD, who had not started taking antibiotics, participated in the study. People in the study were on average 69 years old and most were female (78
Objectives: This study aimed to examine the efficacy of whole genome sequencing (WGS) in accurately predicting susceptibility profiles, potentially eliminating the need for conventional phenotypic drug susceptibility testing (pDST) for first-line antituberculosis drugs in routine tuberculosis diagnosis. Methods: Over the period of 2017 to 2020, 1114 Mycobacterium tuberculosis complex isolates were collected with drug susceptibility testing conducted using the MGIT960 system and WGS performed for predicting drug resistance profiles. In addition, we implemented a new algorithm with an updated WGS workflow, omitting pan-susceptible strains from pDST. Results: Results showed that out of 1075 analysed isolates, WGS-based genotypic sensitivity predictions for isoniazid, rifampicin, ethambutol, and pyrazinamide were 100% (95% CI, 99.6-10 0%), 100% (95% CI, 99.62-10 0%), 99.8% (95% CI, 99.26-99.94%), and 100% (95% CI, 99.63-10 0%), respectively. In contrast, the WGS-based genotypic resistance prediction, was 98.85% (95% CI, 93.77-99.79%) for isoniazid, 94.74% (95% CI, 82.71-98.54%) for rifampicin, 86.96% (95% CI, 67.87-95.46%) for ethambutol, and 75.7% (95% CI, 59.9-86.63%) for pyrazinamide. Moreover, WGS enabled the implementation of a new testing algorithm that made it unnecessary to perform pDST in 954 of all 1075 samples (88.7%) and in 890 of 901 pan- susceptible samples (98.8%). Discussion: Integrating WGS into tuberculosis management offers significant potential to replace phenotypic drug susceptibility testing, especially for problematic drugs like pyrazinamide and ethambutol, potentially improving treatment outcomes. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Anecdotal information suggests that clinical practice regarding the use of putative hepatoprotective agents in TB treatment varies across countries in the WHO European Region.Between November 2023 and May 2024, we conducted a standardised questionnaire survey on the use of putative hepatoprotective agents in patients receiving TB treatment among Tuberculosis Network European Trials Group (TBnet) representatives in countries in the WHO European Region.We received valid responses from 37 of 53 countries (69.8%), with 16 (43.2%) reporting regular use of putative hepatoprotective agents during anti-TB treatment. Half of these countries ( n = 8) are part of the former Soviet Union. In five countries, these agents are recommended by national guidelines. The most commonly used hepatoprotective agents were silibin/silymarin ( n = 9, 56.3%), ursodeoxycholic acid ( n = 5, 31.3%), and soy phospholipids ( n = 4, 25.0%). Treatment duration varied, with 56.3% ( n = 9) using them for less than 1 month, 18.8% ( n = 3) for 1–3 months, and 18.8% ( n = 3) for 4–6 months.Putative hepatoprotective agents are widely used as an adjunct to TB treatment in the WHO European Region, particularly in the countries of the former Soviet Union, some of which have included them in their national guidelines.
Even if in the past years new effective, safe, and orally administrable drugs are available to create shorter regimens, drug-resistant (DR) tuberculosis (TB) treatment remains a critical issue and a major challenge faced by clinicians worldwide. We present the first case of transborder pulmonary pre-extensively drug-resistant (pre-XDR)-TB treated in Italy with the bedaquiline-pretomanid-linezolid regimen. Diagnosis and treatment were started in Ukraine, and, after a month of treatment, due to the Russo-Ukrainian war, the patient moved to Italy, where the diagnosis was confirmed both by genotypic and phenotypic drug susceptibility tests, and treatment continued. In this short report, we highlight challenges and future opportunities to improve the clinical management of patient with DR-TB.
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. Participating centres collected consecutive, detailed individual data for extensively drug-resistant tuberculosis patients. Data were analysed with meta- and regression methods, accounting for between-country heterogeneity. Findings:Among 11,003 patients with multidrug-resistant/rifampicin-resistant tuberculosis, 188 (1·7%) from 16 countries had extensively drug-resistant tuberculosis. Of these, 48·4% harboured strains with resistance to bedaquiline (n = 91/188), 34·0% to linezolid (n = 64/188), and 17·6% to both (n = 33/188). The individual composition of anti-tuberculosis regimens was highly variable, with 151 different drug combinations. Among the 156/188 (83·0%) patients with available treatment outcomes, the pooled percentage of successful outcomes was 40·2% (95% confidence interval [95% CI] 28·4%-53·2%). In patients with unsuccessful treatment outcomes (101/156), most experienced treatment failure (n = 57/156 [pooled proportion 37·1%], 95% CI: 26·1%-49·7%) or death (n = 30/156 [pooled proportion 21·3%], 95% CI: 15·7%-28·2%). After adjustment for disease severity, each additional likely effective drug decreased the odds of unsuccessful outcomes (adjusted odds ratio: 0·65, 95% CI: 0·45-0·96) (p = 0·026), whereas being treated in an upper-middle-income country increased the odds of unsuccessful outcomes compared with being treated in a high-income country (adjusted odds ratio: 13·7, 95% CI: 3·7-50·2) (p < 0·001). Compared with other levels of drug resistance, treatment outcomes were significantly worse for extensively drug-resistant tuberculosis. Interpretation:Only four out of ten patients affected by extensively drug-resistant tuberculosis achieved successful treatment outcomes. These findings highlight the need for adequate, individualised treatment regimens and optimised drug susceptibility testing. Funding:None.
Post-tuberculosis lung disease (PTLD) is an increasingly recognized condition that significantly affects survivors' quality of life, creating disability and incrementing the risk of mortality. PTLD includes a spectrum of structural and functional lung impairments such as obstructive, restrictive, and mixed patterns, bronchiectasis, and pulmonary fibrosis that persist beyond microbiological cure. Global prevalence data highlight a heavy burden of PTLD, especially in high-incidence regions, driven by late diagnosis and suboptimal treatment. Functional and radiological evaluation remains critical for timely diagnosis, with spirometry and imaging revealing lasting abnormalities in a large proportion of TB survivors. Multidisciplinary care is essential and includes bronchodilator therapy, infections/complications management and prevention, pulmonary rehabilitation, and, in selected cases, surgical intervention. Despite increasing recognition, standardized diagnostic and therapeutic pathways for PTLD are still lacking, and data on optimal follow-up, rehabilitation strategies, and preventive measures remain limited. Prospective studies, better stratification tools, and patient education initiatives are urgently needed to reduce PTLD morbidity and mortality. This narrative review synthesizes current evidence on PTLD epidemiology, clinical evaluation and management while offering practical suggestions for clinicians taking care of people with TB and addressing research needs.
[This corrects the article DOI: 10.1371/journal.pgph.0001788.].
Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents. Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics. Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-a inhibitors were high, especially for older TNF-a inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-a inhibitors than for other biologic classes (79% vs. 34%). Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-a inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics.
Non-tuberculous mycobacteria (NTM) account for high clinical burden, and treatment can be challenging. Moreover, accessibility of NTM medications varies across centers. These challenges may lead to unplanned therapeutic changes, discontinuations, potentially affecting patient outcomes. Aim of this survey was to evaluate the accessibility of NTM-targeting drugs in Italy (with a particular focus on clofazimine) in centers associated with the IRENE Registry, a collaborative network of healthcare professionals. A cross-sectional, internet-based, questionnaire-survey on the use and availability of clofazimineand other NTM-targeting drugs was sent to 88 principal investigators of the IRENE network in Italyin 2020. The questionnaires were designed with closed-ended and open-ended questions and distributed using the SurveyMonkey® platform. The surveys underscore the more frequent involvement of pulmonologists (42