Factors Associated with Non-Adherence to Treatment Among Migrants with MDR-TB in Wuhan, China: A Cross-Sectional Study.

Background: Multidrug resistant tuberculosis (MDR-TB) has attracted increasing attention in achieving the global goal of tuberculosis (TB) control. China has the second largest TB burden worldwide and has been experiencing large-scale domestic migration. This study aims to explore the effect of migrants on non-adherence to MDR-TB treatment. Materials and Methods: A cross-sectional study was carried out in Wuhan, China. The exposure cases were migrants who were not locally registered in the residence registration system. The control cases were local residents. Non-adherence cases were patients who were lost follow-up or refused treatment. Chi-square and t-test were used to compare variables between migrants and local residents. Logistic regression models using enter method were used to determine the relationship between migration and non-adherence to treatment. Moderation and medication effects on the association between migrant status and non-adherence were also explored. Results: We studied 73 migrants and 219 local residents. The migrants, who did not to adhere to treatment (55, 75.3%), was far higher than that of local residents (89, 40.6%). Migrants with MDR-TB had 10.38-times higher difficulty in adhering to treatment (adjusted OR = 10.38, 95% CI 4.62-25.28) than local residents. This additional likelihood was moderated by age and treatment registration group. Migration had an indirect association with non-adherence to treatment via social medial insurance (adjusted OR = 1.05, 95% CI 1.01-1.13). Conclusion: There a significant increased likelihood of non-adherence to treatment among migrants with MDR-TB, highlighting the importance of improving treatment adherence in this population. Migration prevented migrants from gaining access to social medical insurance and indirectly reduced their likelihood of adherence to treatment.

Tubercular Osteomyelitis of Navicular Bone: A Rare Site for Bone Tuberculosis.

Introduction: Tuberculosis (TB) is a global public health problem, endemic to India. Osteoarticular TB uncommonly presents in the foot, navicular osteomyelitis is an extremely rare entity. Case Report: We report a rare case of navicular osteomyelitis caused by TB in a 37-year-old man who presented to OPD with swelling and dull aching pain over the dorsum of his left foot. A radiograph of the foot showed a lytic lesion in the navicular bone. Further investigations in the form of aspiration cytology, cartridge-based nucleic acid amplification test, and acid-fast bacilli culture confirmed TB. Category-1 anti-tubercular therapy was started immediately and the patient was treated conservatively. Four drugs (HRZE) were given for 2 months and 3 drugs (HRE) for 9 months, after which the patient stopped his medications on his own. Radiographs and CEMRI at 14-month follow-up showed a healed lesion. Conclusion: This case illustrates an exceptional location of osteoarticular TB and shows that Navicular TB can be treated conservatively with near-complete function and recovery if diagnosed early.

Novel role of cardiovascular MRI to contextualise tuberculous pericardial inflammation and oedema as predictors of constrictive pericarditis.

Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome have reached epidemic proportions, particularly affecting vulnerable populations in low- and middle-income countries of sub-Saharan Africa. TB pericarditis is the commonest cardiac manifestation of TB and is the leading cause of constrictive pericarditis, a reversible (by surgical pericardiectomy) cause of diastolic heart failure in endemic areas. Unpacking the complex mechanisms underpinning constrictive haemodynamics in TB pericarditis has proven challenging, leaving various basic and clinical research questions unanswered. Subsequently, risk stratification strategies for constrictive outcomes have remained unsatisfactory. Unique pericardial tissue characteristics, as identified on cardiovascular magnetic resonance imaging, enable us to stage and quantify pericardial inflammation and may assist in identifying patients at higher risk of tissue remodelling and pericardial constriction, as well as predict the degree of disease reversibility, tailor medical therapy, and determine the ideal timing for surgical pericardiectomy.

Extrapulmonary tuberculosis presenting as hemorrhagic pleuro-pericardial effusions with pericardial mass.

Key Clinical Message: Tuberculosis (TB) pericarditis, while uncommon, should be considered in patients with pericardial masses and effusion. Timely recognition and treatment with anti-TB medications are crucial for a successful outcome. Abstract: TB pericarditis presenting as a pericardial mass is an unusual and rare manifestation of this disease. We report a 59-year-old South Asian male who presented with a 1-week history of dyspnea and cough. He was found to have a hemorrhagic pericardial mass with a massive pericardial effusion. Pleural fluid analysis was positive for TB. The patient was successfully treated with anti-TB medications. Although rare, tuberculous pericardial involvement should be suspected in patients presenting with symptoms of pericardial masses and effusion.

Momentum of hope: The journey toward a universal TB vaccine.

In addressing the persistent threat of tuberculosis (TB) - a disease that claims millions of lives, especially in low-income countries - this correspondence underlines the critical role of advancing vaccine research. Historically, the BCG vaccine, developed over a century ago, has been the cornerstone of TB prevention. However, its efficacy is limited, particularly in adults and against pulmonary TB, the most common form of the disease. Recent developments, such as the M72/AS01E vaccine, demonstrate promising results in increasing protection against TB in adults with latent infections. These advancements represent a significant leap forward in the quest to control and eventually eradicate TB. This piece highlights the necessity of continued investment in vaccine research and development. The pursuit of more effective TB vaccines, capable of providing broader protection across all age groups, is paramount. This effort not only aligns with the WHO's End TB Strategy but also offers hope for a future where TB is no longer a global health crisis.

Gendered gaps to tuberculosis prevention and care in Kenya: a political economy analysis study.

BACKGROUND: Tuberculosis (TB) remains a public health concern in Kenya despite the massive global efforts towards ending TB. The impediments to TB prevention and care efforts include poor health systems, resource limitations and other sociopolitical contexts that inform policy and implementation. Notably, TB cases are much higher in men than women. Therefore, the political economy analysis (PEA) study provides in-depth contexts and understanding of the gender gaps to access and successful treatment for TB infection. DESIGN: PEA adopts a qualitative, in-depth approach through key informant interviews (KII) and documentary analysis. SETTING AND PARTICIPANTS: The KIIs were distributed among government entities, academia, non-state actors and community TB groups from Kenya. RESULTS: The themes identified were mapped onto the applied PEA analysis framework domains. The contextual and institutional issues included gender concerns related to the disconnect between TB policies and gender inclusion aspects, such as low prioritisation for TB programmes, limited use of evidence to inform decisions and poor health system structures. The broad barriers influencing the social contexts for TB programmes were social stigma and cultural norms such as traditional interventions that negatively impact health-seeking behaviours. The themes around the economic situation were poverty and unemployment, food insecurity and malnutrition. The political context centred around the systemic and governance gaps in the health system from the national and devolved health functions. CONCLUSION: Broad contextual factors identified from the PEA widen the disparity in targeted gender efforts toward men. Following the development of effective TB policies and strategies, it is essential to have well-planned gendered responsive interventions with a clear implementation plan and monitoring system to enhance access to TB prevention and care.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Performance of the BD MAX MDR-TB assay in a clinical setting and its impact on the clinical course of patients with pulmonary tuberculosis: a retrospective before-after study.

Background: Missing isoniazid (INH) resistance during tuberculosis (TB) diagnosis can worsen the outcomes of INH-resistant TB. The BD MAX MDR-TB assay (BD MAX) facilitates the rapid detection of TB and INH and rifampin (RIF) resistance; however, data related to its performance in clinical setting remain limited. Moreover, its effect on treatment outcomes has not yet been studied. Methods: We compared the performance of BD MAX for the detection of INH/RIF resistances to that of the line probe assay (LPA) in patients with pulmonary TB (PTB), using the results of a phenotypic drug sensitivity test as a reference standard. The treatment outcomes of patients who used BD MAX were compared with those of patients who did not. Results: Of the 83 patients included in the study, the BD MAX was used for an initial PTB diagnosis in 39 patients. The sensitivity of BD MAX for detecting PTB was 79.5%. The sensitivity and specificity of BD MAX for INH resistance were both 100%, whereas these were 50.0% and 95.8%, respectively, for RIF resistance. The sensitivity and specificity of BD MAX were comparable to those of LPA. The BD MAX group had a shorter time interval from specimen request to the initiation of anti-TB drugs (2.0 days vs. 5.5 days, p=0.001). Conclusion: BD MAX showed comparable performance to conventional tests for detecting PTB and INH/RIF resistances. The implementation of BD MAX as a diagnostic tool for PTB resulted in a shorter turnaround time for the initiation of PTB treatment.

Inhibitors of the Thioesterase Activity of Mycobacterium tuberculosis Pks13 Discovered Using DNA-Encoded Chemical Library Screening.

DNA-encoded chemical library (DEL) technology provides a time- and cost-efficient method to simultaneously screen billions of compounds for their affinity to a protein target of interest. Here we report its use to identify a novel chemical series of inhibitors of the thioesterase activity of polyketide synthase 13 (Pks13) from Mycobacterium tuberculosis (Mtb). We present three chemically distinct series of inhibitors along with their enzymatic and Mtb whole cell potency, the measure of on-target activity in cells, and the crystal structures of inhibitor-enzyme complexes illuminating their interactions with the active site of the enzyme. One of these inhibitors showed a favorable pharmacokinetic profile and demonstrated efficacy in an acute mouse model of tuberculosis (TB) infection. These findings and assay developments will aid in the advancement of TB drug discovery.

Assessing potential drug-drug interactions between clofazimine and other frequently used agents to treat drug-resistant tuberculosis.

Clofazimine is included in drug regimens to treat rifampicin/drug-resistant tuberculosis (DR-TB), but there is little information about its interaction with other drugs in DR-TB regimens. We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone. Newly diagnosed adults with DR-TB at Klerksdorp/Tshepong Hospital, South Africa, were started on the then-standard treatment with clofazimine temporarily excluded for the initial 2 weeks. Pharmacokinetic sampling was done immediately before and 3 weeks after starting clofazimine, and drug concentrations were determined using validated liquid chromatography-tandem mass spectrometry assays. The data were interpreted with population pharmacokinetics in NONMEM v7.5.1 to explore the impact of clofazimine co-administration and other relevant covariates on the pharmacokinetics of isoniazid, linezolid, levofloxacin, and cycloserine. Clofazimine, isoniazid, linezolid, levofloxacin, and cycloserine data were available for 16, 27, 21, 21, and 6 participants, respectively. The median age and weight for the full cohort were 39 years and 52 kg, respectively. Clofazimine exposures were in the expected range, and its addition to the regimen did not significantly affect the pharmacokinetics of the other drugs except levofloxacin, for which it caused a 15% reduction in clearance. A posteriori power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at P < 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring.

Novel automated AIMLAM for diagnosis of Mycobacterium tuberculosis.

Aim: A rapid and precise diagnostic method is crucial for timely intervention and management of tuberculosis. The present study compared the diagnostic accuracy of a novel lipoarabinomannan (LAM) antigen test, AIMLAM, for tuberculosis in urine samples. Methodology: The study subjected 106 TB suspects to smear microscopy, MGIT, GeneXpert and AIMLAM. Results: Among 106, smear microscopy identified 36 as positive (33%) (sensitivity; 70.93%, 95% CI (60.14-80.22%), while MGIT showed 38 positive (36.8%). GeneXpert detected 59 positives (sensitivity; 96.83, 95% CI (89.00-99.61%)). AIMLAM declared 61 as positive (57.5%) (sensitivity; 100.00, 95% CI (94.13-100.00%) and 45 as negative (42.5%). Conclusion: Overall, AIMLAM demonstrated better diagnostic accuracy than GeneXpert Assay, smear microscopy and MGIT liquid culture in urine samples.

This study describes a new way to detect tuberculosis, called AIMLAM. Unlike traditional methods that use sputum or blood, AIMLAM tests urine samples and bodily fluids. It is automated and uses easily accessible samples to identify a tuberculosis infection, so may be a convenient and noninvasive option for healthcare providers. The test shows promising results in terms of accuracy and sensitivity.

Green- and Blue-Emitting Tb3+-Activated Linde Type A Zeolite-Derived Boro-Aluminosilicate Glass for Deep UV Detection/Imaging.

Tb3+-activated LTA zeolite-derived boro-aluminosilicate glass samples with a composition of xTb2O3-68(Na2O-Al2O3-SiO2)-32B2O3 (x = 0.2, 1.0 and 10 extra wt%) were prepared using the melt-quenching method. The emission spectra recorded upon ultraviolet (UV) excitation with two different wavelengths of 193 and 378 nm showed blue light (5D3 to 7FJ=6,5,4 and 5D4 to 7F6 transitions of Tb3+) and green light (5D4 to 7F5 transition of Tb3+) emissions with comparable intensities up to a Tb3+ concentration of 10 extra wt%. Of note, the mean decay times of the green luminescence of the glass samples were relatively fast (<20 µs). The synthesized glass has potential in applications concerning UV imaging, UV detection, and plasma display panels.

Vigilance Needed in Treating a Child with Disseminated TB: A Case Report.

BACKGROUND: Tuberculosis is still one of the biggest causes of infection-related death around the world. Disseminated tuberculosis is a potentially fatal disease caused by the haematogenous spread of Mycobacterium tuberculosis. First-line anti-tuberculosis drugs in-clude isoniazid, rifampicin, pyrazinamide, and ethambutol. The first three drugs are known to cause hepatotoxicity. CASE PRESENTATION: We have, herein, reported a case of Drug-induced Liver Injury (DILI) due to anti-tuberculosis therapy in a one-year-old male child with disseminated tuberculosis. He was started on a fixed-dose combination of Anti-tuberculosis Therapy (ATT; isoniazid 50 mg, rifampicin 75 mg, and pyrazinamide 150 mg) and pyridoxine 10 mg orally. Initially, liver pa-rameters were normal, but later on with the course of the treatment, there was a rapid rise in liver enzymes, suggesting liver injury. DISCUSSION: The association between liver injury and anti-tuberculosis therapy has been con-firmed by applying various causality association scales. It is obvious that proper treatment of disseminated tuberculosis can avoid the development of drug-resistant strains that can be harm-ful, worsening the prognosis as there are fewer therapeutic alternatives available. At the same time, there is a need to monitor the patient with ATT-induced DILI. CONCLUSION: The diagnosis of tuberculosis in children is difficult because of the mild, nonspe-cific clinical presentation, which usually reflects the implicated underlying organ. In addition to prompt diagnosis and treatment of disseminated TB, careful monitoring is equally important.

TB LAMP assay, a beneficial tool for the diagnosis of Tubercular meningitis in resource-limited settings.

INTRODUCTION: Tubercular meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological sequelae. The estimated mortality due to TBM in India is 1.5 per 100,000 population. In resource-limited settings, only the Ziehl-Neelsen (ZN) stain, which has very little sensitivity, is available. The World Health Organization recommended the Loop Mediated Isothermal Amplification (TB LAMP) assay for pulmonary tuberculosis only. We evaluated this test for tubercular meningitis as well. METHODOLOGY: In a cross-sectional study of 2-year duration, we have taken 239 cerebrospinal fluid samples from suspected cases of tubercular meningitis patients. ZN staining along with Mycobacteria Growth Indicator Tube (MGIT) TB culture, Xpert MTB/RIF Ultra assay, and commercial TB LAMP assay were performed for each sample. RESULTS: Out of 239 samples, 40 samples (16.73%) were found TB LAMP assay positive, 48 samples (20.08%) were found Xpert ultra-assay positive, 12 samples (5.02%) were MGIT TB culture positive and acid-fast bacillus smear positive in ten samples (4.18 %). Out of 12 MGIT-positive samples, all samples (100%) were TB LAMP and Xpert ultra positive and one sample (8.33%) was ZN smear positive. In 199 negative samples from the TB LAMP assay, eight samples were positive by Xpert, none by MGIT TB culture and AFB smear. Sensitivity and specificity were found as 100% and 87.66%, respectively, for the TB LAMP assay. CONCLUSION: TB LAMP assay is a rapid, cost-effective, sensitive, and specific test for tubercular meningitis infection in resource-limited settings.

Patterns and profiles of drug resistance-conferring mutations in Mycobacterium tuberculosis genotypes isolated from tuberculosis-suspected attendees of spiritual holy water sites in Northwest Ethiopia.

Purpose: This study examined the patterns and frequency of genetic changes responsible for resistance to first-line (rifampicin and isoniazid), fluoroquinolones, and second-line injectable drugs in drug-resistant Mycobacterium tuberculosis (MTB) isolated from culture-positive pulmonary tuberculosis (PTB) symptomatic attendees of spiritual holy water sites (HWSs) in the Amhara region. Patients and methods: From June 2019 to March 2020, a cross-sectional study was carried out. A total of 122 culture-positive MTB isolates from PTB-suspected attendees of HWSs in the Amhara region were evaluated for their drug resistance profiles, and characterized gene mutations conferring resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs), and second-line injectable drugs (SLIDs) using GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0. Drug-resistant MTB isolates were Spoligotyped following the manufacturer's protocol. Results: Genetic changes (mutations) responsible for resistance to RIF, INH, and FLQs were identified in 15/122 (12.3%), 20/122 (16.4%), and 5/20 (25%) of MTB isolates, respectively. In RIF-resistant, rpoB/Ser531Lue (n = 12, 80%) was most frequent followed by His526Tyr (6.7%). Amongst INH-resistant isolates, katG/Ser315Thr1 (n = 19, 95%) was the most frequent. Of 15 MDR-TB, the majority (n = 12, 80%) isolates had mutations at both rpoB/Ser531Leu and katG/Ser315Thr1. All 20 INH and/or RIF-resistant isolates were tested with the MTBDRsl VER 2.0, yielding 5 FLQs-resistant isolates with gene mutations at rpoB/Ser531Lue, katG/Ser315Thr1, and gyrA/Asp94Ala genes. Of 20 Spoligotyped drug-resistant MTB isolates, the majority (n = 11, 55%) and 6 (30%) were SIT149/T3-ETH and SIT21/CAS1-Kili sublineages, respectively; and they were any INH-resistant (mono-hetero/multi-). Of 15 RIF-resistant (RR/MDR-TB) isolates, 7 were SIT149/T3-ETH, while 6 were SIT21/CAS1-Kili sublineages. FLQ resistance was detected in four SIT21/CAS1-Kili lineages. Conclusion: In the current study, the most common gene mutations responsible for resistance to INH, RIF, and FLQs were identified. SIT149/T3-ETH and SIT21/CAS1-Kili constitute the majority of drug-resistant TB (DR-TB) isolates. To further understand the complete spectrum of genetic changes/mutations and related genotypes, a sequencing technology is warranted.

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

Evaluating tuberculosis treatment outcomes in Haiti from 2018 to 2019: A competing risk analysis.

Objectives: This study assesses tuberculosis (TB) treatment outcomes in Haiti. Methods: Data from drug-susceptible patients with TB (2018-2019) were analyzed using the Fine & Gray model with multiple imputation. Results: Of the 16,545 patients, 14.7% had concurrent HIV coinfection, with a 66.2% success rate. The median treatment duration was 5 months, with patients averaging 30 years (with an interquartile range of 22-42 years). The estimated hazard of achieving a successful treatment outcome decreased by 2.5% and 8.1% for patients aged 45 and 60 years, respectively, compared with patients aged 30 years. Male patients had a 6.5% lower estimated hazard of success than their female counterparts. In addition, patients coinfected with HIV experienced a 35.3% reduction in the estimated hazard of achieving a successful treatment outcome compared with those with a negative HIV serologic status. Conclusions: Integrated health care approaches should be implemented, incorporating innovative solutions, such as machine learning algorithms combined with geographic information systems and non-conventional data sources (including social media), to identify TB hotspots and high-burden households.

WHO's end of TB targets: unachievable by 2035 without addressing under nutrition, forced displacement, and homelessness: trend analysis from 2015 to 2022.

Tuberculosis (TB) remains a significant global health challenge, despite the World Health Organization (WHO) actively working towards its eradication through various initiatives and programs. Undernutrition, forced displacement, and homelessness worsen TB's burden and challenge control efforts; however, there is still no adequate research that shows the trend of these underlying factors to attain the WHO's ambitious TB targets. So, this study aims to analyze the trend analysis of these underlying factors worldwide from 2015 to 2022 and their impact on the feasibility and implications of reaching the End TB targets by 2035. We utilized international databases, including UNHCR, FAO, and WHO reports, as secondary data sources. Data were extracted chronologically from 2015 to 2022 to illustrate trends in undernutrition, forced displacement, and homelessness on a global level.This trend analysis reveals that undernutrition, forced displacement, and homelessness have worsened over time. Undernutrition rose from 8.4 to 9.8% globally between 2015 and 2021, affecting 22.7 million additional individuals each year. In 2022, undernutrition affected 735 million people globally. Africa (21.9%) and Asia (10.6%) had the highest rates, while Western Europe and North America had lower rates than the global average: 3.4% and 2.5%, respectively.Similarly, the global rate of forced displacement increased from 65.1 million people in 2015 to 108.4 million in 2022, a 21% increase from 2021. This means that an extra 19 million people were displaced in 2021. Globally, homelessness, affecting 1.6 billion people, has worsened over time. Despite being a highly vulnerable group to TB, homeless individuals are often neglected in TB control efforts. Our findings underscore the critical importance of addressing undernutrition, forced displacement, and homelessness in achieving the World Health Organization's ambitious End TB targets by 2035, as highlighted through trend analysis from 2015 to 2022. Implementing policies focusing on nutrition, stable housing, and the challenges faced by displaced populations is imperative for progress toward a TB-free world.

QuantiFERON-TB reversion in children and adolescents with tuberculosis.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.