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.

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript.

BACKGROUND:Human migration and the ever-changing geopolitical scenarios are redefining the epidemiology and the management of tuberculosis (TB), especially in low-TB burden countries welcoming high rates of people from high-TB burden countries.METHODS:We conducted an observational retrospective mono-centric study in a Northern-Italy TB reference centre from 1 January 1990 to 31 December 2019, focusing on the differences in epidemiology, resistance patterns and treatment outcomes between Italians and migrants with active TB. Data were collected from medical records.RESULTS:A total of 10555 patients were included, 4614 Italians and 5941 migrants. Among migrants, higher rates of rifampin-resistant (RR) or multidrug-resistant (MDR) TB were reported, as well as higher rates of loss to follow-up. Among Italians, higher mortality rates and a higher number of extrapulmonary TB cases were found.CONCLUSION:Our study describes one of the largest cohorts of patients with active TB in Italy, highlighting the need for tailored approaches in native and migrant populations.

Background:The Coronavirus (COVID-19) pandemic significantly impacted on tuberculosis (TB) services (TB) services in both high and low TB burden countries. Objectives: This study aimed to investigate the impact of COVID-19 on TB outpatient services in terms of new TB case notifications and treatment outcomes in a rural area of Senegal. Methods:A retrospective observational study was conducted at the Health Care Centre of Diofior (HCD) in the Fimela district, Fatick Region (Senegal), covering the period from January 1st, 2018, to December 31st, 2022. Data were divided into pre-COVID-19 (until March 31st, 2020) and during-COVID-19 (from April 1st, 2020) periods for analysis. Results:Among the 246 TB cases included (63.4% male, median age 38.4 years), 94 (38.2%) had been diagnosed in the pre-COVID-19 period and 152 (61.8%) in the during-COVID-19 period. In 2020, TB case notifications dropped by 24.4% compared to 2019, followed by an increase of 70.6% in 2021 and 91.2% in 2022. The TB treatment success rate decreased from 85.1% before COVID-19 to 77.6% in during-COVID-19 period. Moreover, mortality increased from 2.1% to 5.3%, and the lost-to-follow-up rate rose from 8.5% to 14.5% between the pre- and during-COVID-19 periods. Conclusions:Although the number of COVID-19 cases reported in Senegal was relatively low in the study period compared to other settings, our study indicates that the pandemic had a significant impact on TB services in this rural area of Senegal.

Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.

Background: Tuberculosis (TB) unevenly affects individuals across the globe, especially in rural areas of low-income countries. Aim of the study was to assess the impact of social protection to increase TB awareness on treatment outcomes among TB patients in a rural area of Senegal. Materials & methods: The study, conducted in Fimela district (Senegal) from 1 January 2010 to 31 December 2019 and the intervention started from 31 January 2013, includes activities to increase awareness, active case finding, active follow-up and social protection. Results: Overall, 435 subjects - mainly male and young - were included in the analysis. Among TB cases, 94% had pulmonary involvement, 87% had no previous TB history, and 6% resulted positive HIV. Improved outcome was observed once intervention began (from 71 to 91%, p < 0.001); whereas mortality decreased (from 15 to 5%; p < 0.001), especially for those HIV co-infected for whom TB mortality rate dropped from 70 to 29%. Conclusion: After beginning the cooperation program, TB treatment success increased as a result of the decline of mortality, especially in people living with HIV.

Summary Despite notable progresses in the recent decades, tuberculosis (TB) continues to remain a public health concern even in Europe. TB prevention and care should be people-centred, improving ambulatory models across countries, in order to expand access to diagnosis and treatment for both TB infection and disease. Even more, during emergencies such as the current pandemic, when seeking of TB care has been replaced by the fear of coronavirus disease 2019 (COVID-19), TB patient’s care is fundamental. In this short communication, we document how was possible to implement a TB outpatient service meanwhile a local outbreak of SARS-CoV-2 transmission was ongoing.

The emerge of drug-resistant tuberculosis (TB) strain in recent decades is hampering the efforts of the international community to eliminate the disease worldwide. The World Health Organization (WHO) has drafted many strategies to achieve this ambitious goal. In the very beginning, the aim was to standardize inadequate regimens used in many countries and, thereafter, evolved to tackle the social determinants which hinder TB elimination. However, following the path of narrowing the clinical vision to deal with TB, there is an increased need to personalize the treatment considering both patients and pathogen unique characteristics. In our narrative review, we report the advantages and the backwards in developing a method to implement the concept of precision medicine to the treatment of TB. In this dissertation, we highlight the importance to address different aspects of the diseases encompassing the host and pathogen features, as well as the needs to further implement an adequate follow-up based on the available resources. Nevertheless, many things may hamper the vision of precision medicine in TB, such as the complexity and the costs to develop novel compounds and the costs related to global-scale implementation of patient-centered follow-up. To achieve the ambitious goal of TB elimination, a radical change in TB treatment is needed in order to give a more comprehensive approach based both on patients' peculiarities and driven by drug susceptibility tests and whole-genome sequencing.

World Tuberculosis Day, observed on 24 March each year, is the global call to raise awareness, celebrate successes and remind the world that tuberculosis (TB) is still the number one killer among the infectious causes of death [1]. TB is a preventable and curable disease, and its control is a highly cost-effective health intervention. However, diagnostic delay and inadequate treatment contribute to the severity and mortality of the disease as well as the risk of transmission and development of drug resistance. Despite the fact that TB disproportionately impacts low- and middle-income countries, it does not spare any country in the world, including those in the European Union/European Economic Area, where more than 4000 people still die from the disease every year [2]. Moreover, the high number of multidrug-resistant (MDR)-TB cases in some countries of the World Health Organization (WHO) European Region poses a growing public health threat. Despite the sheer numbers, TB has for too long been overshadowed by HIV and malaria, and currently by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) epidemic. TB remains a global health emergency https://bit.ly/39DqHTb

COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients' ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm3) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.

Abstract Tuberculosis (TB) and humans have coexisted for more than 40,000 years. Tb is an ancient and dangerous disease for the world population. The international community has developed new tools for early detection but TB strains evolved acquiring resistance to first-line therapeutic drugs and the difficulties of treatment have increased. Furthermore, TB has formed also an alliance with human immunodeficiency virus; in this way the poorest populations were most affected. The current vaccine planning activity includes 14 new vaccines against tb (11 of those in the phaseII/III) developed with different techniques. Now, however, new antiTB drugs and new antiTB regimens are urgently requested; it is good that scientific research grows but universal health care and social protection is necessary and fundamental to eliminate TB. Actions are needed to improve the quality of life of patients and their families to stop tuberculosis and its link with poverty.

Clofazimine (CFZ), an old hydrophobic riminophenazine, has a wide range of antimycobacterial activity ranging from leprosy to nontuberculous mycobacterial diseases. CFZ has several advantages such as a favorable pharmacokinetic profile, dose-dependent side effects as well as low price. In this narrative review, we have assessed the clinical development of CFZ, starting from the potential in vitro mechanism of actions, to the spectrum of side effects and potential drug-drug interactions, highlighting its current place in therapy and future possible use in leprosy, nontuberculous mycobacterial diseases and drug-resistant tuberculosis.

M. MARTINI, N. RICCARDI, A. GIACOMELLI, V. GAZZANIGA, G. BESOZZI 1 Department of Health Sciences, University of Genoa, Italy; UNESCO Chair “Anthropology of Health Biosphere and Healing System”, University of Genoa, Italy; StopTB Italia Onlus, Milan, Italy; Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; III Infectious Disease Unit, ASST-FBF-Sacco, Milan, Italy; Department of Biomedical and Clinical Sciences, L. Sacco, University of Milan, Italy; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy; President of Italian Society of Human Sciences in Medicine (SISUMed), Rome Italy; Villa Marelli Insitute, Niguarda Ca’ Granda Hospital, Milan, Italy

Tuberculosis (TB) and humans have coexisted for more than 40,000 years. The word "tuberculosis" derives from "tubercle", the histological lesion which appears in the organs, described by Pott in the late Eighteenth century and found, by molecular biology, in human skeletons dating back to 5000 BC. Early description of TB can be found in the writings of ancient India and China and in the Bible. In ancient Greece tuberculosis was not considered contagious, but Aristotle recognized the contagious nature of the pig's and ox's scrofula. The suspicion that phthisis is a contagious disease and that isolation can reduce the risk of transmission was expressed for the first time by the Arabian Avicenna, in his work "The canon of medicine". In 1699, the Health Council of the Republic of Lucca founded the "sanatorium" concept as place of care and isolation. In 1865 Villemain inoculated tubercular material from a human lymph node into a rabbit, obtaining for the first time the typical tubercular lesions. Some years later, on March 24, 1882, Robert Koch announced to the Berlin Society of Physiology the discovery of Mycobacterium tuberculosis. In the same period Virchow improved awareness of risk factors and correct behaviours among the general population. In 1952 Waksman won the Nobel Prize for the discovery of the first active drug against TB: streptomycin. Nevertheless, drug resistance appeared rapidly some years later and it is still a great challenge in TB fight nowadays.