Tuberculosis Disease Research Articles

Revisiting tuberculosis diagnosis: the prospect of urine lipoarabinomannan assay as a diagnostic tool in people living with human immunodeficiency virus

Abstract Background Tuberculosis, since its discovery has become a global health burden, continuously spreading across the nations of the earth with increased mortality. Its effect on human immunodeficiency virus (HIV) progression and immune cell deterioration cannot be overlooked. The widespread use of traditional and molecular TB diagnostic methods has been hindered by several factors. Nonetheless, the development of a rapid, sensitive, timely, non-invasive diagnostic protocol could revolutionise the diagnostic era and halt the spread of this infectious agent. It could also help in the early diagnosis of the infection in poorly developed areas. The detection efficacy of urine lipoarabinomannan assay as a prospect in tuberculosis diagnosis in HIV-positive patients was assessed in this study. Urine samples were collected into a wide-mouthed universal container from HIV-positive patients with signs and symptom of tuberculosis and HIV advanced disease. Alere determine urine lateral flow—LAM test was used for the detection of LAM antigen in urine samples of HIV-positive patients. The CD4 count of the HIV-positive patients was also documented. Results A total of 85 HIV-positive subjects were included in the analysis based on the inclusion criteria. Urinary LAM was reactive in 29 (34.1%) of 85 HIV-positive patients and non-reactive in 56 (69.1%). The majority of the participants had a CD4+ count < 200 cells/µL 60 (70.6%), while others had CD4+ count ≥ to 200 cells/µL 25 (29.4%). There was no statistically significant difference between CD4 count and LAM positivity. Most of the affected age groups in the study were 31–45 years, and females had preponderance in comparison to male subjects. Conclusions The use of urinary LAM in HIV-positive patients is a helpful tool for TB screening. It also has a promising ability for early TB diagnosis in the study group and other TB-associated disease conditions in resource-deprived settings. For the general populace, further research is required to certify its sensitivity and specificity.

Association of prior tuberculosis with cardiovascular status in perinatally HIV-1-infected adolescents

BackgroundWhether, and how, co-occurring HIV-1 infection (HIV) and tuberculosis (TB) impact cardiovascular status, especially in adolescents with perinatally acquired HIV (APHIV), have not been examined. We hypothesised that APHIV with...

Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.

Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to the first-line drugs isoniazid and rifampin, is a growing source of global mortality and threatens global control of tuberculosis disease. The diarylquinoline bedaquiline has recently emerged as a highly efficacious drug against MDR-TB and kills Mycobacterium tuberculosis by inhibiting mycobacterialATP synthase. However, themechanisms underlying bedaquiline's efficacy against MDR-TB remain unknown. Here we investigate bedaquiline hyper-susceptibility in drug-resistant Mycobacterium tuberculosis using systems biology approaches. We discovered that MDR clinical isolates are commonly sensitized to bedaquiline. This hypersensitization is caused by several physiological changes induced by deficient catalase activity. These include enhanced accumulation of reactive oxygen species, increased susceptibility to DNA damage, induction of sensitizing transcriptional programs, and metabolic repression of several biosynthetic pathways. In this work we demonstrate how resistance-associated changes in bacterial physiology can mechanisticallyinduce collateral antimicrobial drug sensitivity and reveal druggable vulnerabilities in antimicrobial resistant pathogens.

Risk of mycobacterial infections in a cohort of silicosis patients with autoimmune rheumatic diseases

Objective: To evaluate the incidence rates of mycobacterial infections in silicosis patients with systemic autoimmune rheumatic disease (ARD). Methods: This was a retrospective cohort of silicosis patients between January of 1999 and December of 2023. We compared the incidence of tuberculosis and nontuberculous mycobacterial disease (NTM) in patients with silicosis with and without ARD. We also compared the tuberculosis incidence in the overall cohort with general Brazilian population estimates. Results: The study comprised 369 silicosis patients, of whom 35 (9.5%) had ARD. Having ARD did not affect the cumulative incidence of mycobacterial diseases. The risk of tuberculosis was higher in the cohort when compared with that in the adult Brazilian male population (age-adjusted incidence rate ratio = 20.46; 95% CI 14.89-28.13). Conclusions: In this cohort of patients with silicosis, ARD was not associated with the incidence of mycobacterial diseases.

Active tuberculosis disease among people living with HIV on ART who completed tuberculosis preventive therapy at three public hospitals in Uganda.

Tuberculosis (TB) preventive therapy (TPT) reduces the incidence of TB among people living with the human immunodeficiency virus (PLHIV). However, despite an increase in TPT uptake, TB/HIV coinfection remains stagnant in Uganda especially in areas of increasing HIV incidence such as the Bunyoro sub-region. This study was a retrospective review records (antiretroviral therapy [ART] files) of PLHIV who were active on ART and completed TPT in 2019/2020 at three major hospitals in the Bunyoro sub-region, Uganda: Masindi General Hospital, Hoima Regional Referral Hospital, and Kiryandongo General Hospital. The sample size (987) for each facility was determined using a proportionate sampling method to ensure the study's power and precision. Factors independently associated with acquiring TB disease post TPT were determined using modified Poisson regression analysis. An adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals were reported. The participants' mean age was 38.23 (±11.70) and the majority were female (64.94%). Overall, 9.63% developed active TB disease post TPT completion. In the adjusted analysis, factors associated with active TB disease were a history of an unsuppressed viral load after TPT (aPRR 4.64 (2.85-7.56), p<0.001), opportunistic infections after TPT completion (aPRR 4.31 (aPRR 2.58-7.2), p<0.001), a history of TB active TB disease (aPRR 1.60 (1.06-2.41), p = 0.026), and chronic illness during or after TPT (aPRR 1.68 (1.03-2.73), p = 0.038). To reduce the development of TB disease post TPT thereby improving the effectiveness of TPT, ART adherence should be emphasized to resolve viral suppression and active management of chronic and opportunistic infections. Further clinical management consideration and research is needed for PLHIV who receive TPT but have a previous history of TB disease.

Pregnant women and healthcare workers' perceptions on tuberculosis and screening: a cross-sectional study in Indonesia.

There is a scarcity of studies regarding the obstacles in tuberculosis (TB) screening in pregnant women. This study aimed to assess the perceptions of TB as a disease and TB screening among pregnant women and healthcare workers, describe pregnant women's perceptions on specific TB screening methods and explore associations between the perceptions of TB with the intention to have TB screening by pregnant women. A cross-sectional study was conducted at six primary healthcare centres in Yogyakarta Municipality, Indonesia among 240 pregnant women and 126 healthcare workers interviewed with a structured questionnaire about their perceptions. Perceptions were analysed as percentages and associated factors were tested by multivariable logistic regression. Most pregnant women and healthcare workers supported TB screening in pregnant women based on their perceptions of the susceptibility to or severity of TB and the benefits and risks of TB screening. Women who perceived the high susceptibility of TB disease and the benefits of TB screening were significantly more likely to have high intentions to accept TB screening in the future. Pregnant women's perceptions of TB and TB screening influenced their intention to be screened; however, appropriate testing methods for universal TB screening in pregnant women in areas with a high prevalence of TB require further studies.

Clinical profile, risk factors, disease severity, and outcome for COVID-19 disease in patients with tuberculosis on treatment under the National Tuberculosis Elimination Program: a cohort of 1400 patients.

COVID-19 affected millions of people worldwide, and tuberculosis (TB) continues to affect millions of people each year. The combined pandemic of COVID-19 and TB had a catastrophic effect on healthcare policies and healthcare setups around the globe. The clinical profile and factors affecting the outcome of COVID-19 disease in TB patients on treatment in field conditions have not been studied in detail. The present study attempted to study the occurrence of COVID-19 among patients on TB treatment in terms of severity of COVID-19 disease and outcome of both COVID-19 and TB in patients at National Tuberculosis Elimination Program treatment centers over a period of one year during peak COVID-19 times. Out of 1400 TB patients enrolled, 65 (5%) suffered from COVID-19 disease. Of the 65 TB patients with COVID-19 disease, 37 (57%) were male and under 45 years old, 33 (51%) had a TB diagnosis after first receiving a COVID-19 diagnosis, 29 (45%) had a TB diagnosis first, and received anti-TB treatment before receiving a COVID-19 diagnosis, and only 3 patients (5%) had a COVID-19 and TB diagnosis concurrently. The majority of 59 (91%) patients had mild COVID-19 disease. The outcome of TB treatment was available in 25 patients out of these 65 COVID-19-positive patients, with 21 (84%) patients having a favorable outcome. Out of the 65 COVID-19-positive patients, 4/25 (16%) had unfavorable outcomes, with one patient (4%) failing TB treatment and two patients (8%) dying. This is the first study from India that studied the occurrence and course of COVID-19 among a large number of TB patients taking anti-TB treatment under programmatic conditions. Due to the similarity in symptoms of TB and certain viral respiratory illnesses, a protocol should be established for health care to check patients for both illnesses.

Prevention of stroke and cognitive decline in pediatric population in resource-limited settings

There is an increasing global burden of pediatric stroke especially in low- and middle-income countries (LMICs). This is worsened by the specific risk factors in these areas, including Sickle Cell Disease and endemic infections like Tuberculosis and Human Immunodeficiency disease. Stroke occurs 221–300 times more frequently in patients with SCD when compared to healthy children. Although established stroke units and acute stroke care can improve outcomes, these are often not available in resource-poor settings. Primary and secondary prevention of strokes become a very important strategy to reduce the mortality and debilitating physical and cognitive long-term effects of stroke. There are myriads of challenges with implementing already established global policies and guidelines for stroke care in LMICs. These include paucity of data on this subject, poor knowledge and awareness about the symptoms of childhood stroke, adverse cultural beliefs regarding strokes, lack of screening and diagnostic equipment, inadequately trained manpower as well as nonexistent evidence-based management guidelines in these regions. To address these challenges, simple, cost-effective, stroke care models that determine the process of care and how available services should be delivered have been proposed to suit the peculiarities of LMICs in the areas of stroke risk assessment, prevention, and management.

Leveraging large-scale Mycobacterium tuberculosis whole genome sequence data to characterise drug-resistant mutations using machine learning and statistical approaches

Tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global public health problem, resulting in > 1 million deaths each year. Drug resistance (DR), including the multi-drug form (MDR-TB), is challenging control of the disease. Whilst many DR mutations in the Mtb genome are known, analysis of large datasets generated using whole genome sequencing (WGS) platforms can reveal new variants through the assessment of genotype-phenotype associations. Here, we apply tree-based ensemble methods to a dataset comprised of 35,777 Mtb WGS and phenotypic drug-susceptibility test data across first- and second-line drugs. We compare model performance across models trained using mutations in drug-specific regions and genome-wide variants, and find high predictive ability for both first-line (area under ROC curve (AUC); range 88.3–96.5) and second-line (AUC range 84.1–95.4) drugs. To aggregate information from low-frequency variants, we pool mutations by functional impact and observe large improvements in predictive accuracy (e.g., sensitivity: pyrazinamide + 25%; ethionamide + 10%). We further characterise loss-of-function mutations observed in resistant phenotypes, uncovering putative markers of resistance (e.g., ndh 293dupG, Rv3861 78delC). Finally, we profile the distribution of known DR-associated single nucleotide polymorphisms across discretised minimum inhibitory concentration (MIC) data generated from phenotypic testing (n = 12,066), and identify mutations associated with highly resistant phenotypes (e.g., inhA − 779G > T and 62T > C). Overall, our work demonstrates that applying machine learning to large-scale WGS data is useful for providing insights into predicting Mtb binary drug resistance and MIC phenotypes, thereby potentially assisting diagnosis and treatment decision-making for infection control.

Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.

Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p<0.0001) and presumptive EPTB (0.76 vs 0.54, p = 0.045) when using the MRS. Among HIV-ve participants in an adult cohort in Vietnam, the concentrations of uLAM remained relatively low for people with clinical TB, which may present challenges for improving RDT sensitivity.

Computer vision applications for the detection or analysis of tuberculosis using digitised human lung tissue images - a systematic review

ObjectiveTo conduct a systematic review of the computer vision applications that detect, diagnose, or analyse tuberculosis (TB) pathology or bacilli using digitised human lung tissue images either through automatic or semi-automatic methods. We categorised the computer vision platform into four technologies: image processing, object/pattern recognition, computer graphics, and deep learning. In this paper, the focus is on image processing and deep learning (DL) applications for either 2D or 3D digitised human lung tissue images. This review is useful for establishing a common practice in TB analysis using human lung tissue as well as identifying opportunities for further research in this space. The review brings attention to the state-of-art techniques for detecting TB, with emphasis on the challenges and limitations of the current techniques. The ultimate goal is to promote the development of more efficient and accurate algorithms for the detection or analysis of TB, and raise awareness about the importance of early detection.DesignWe searched five databases and Google Scholar for articles published between January 2017 and December 2022 that focus on Mycobacterium tuberculosis detection, or tuberculosis pathology using digitised human lung tissue images. Details regarding design, image processing and computer-aided techniques, deep learning models, and datasets were collected and summarised. Discussions, analysis, and comparisons of state-of-the-art methods are provided to help guide future research. Further, a brief update on the relevant techniques and their performance is provided.ResultsSeveral studies have been conducted to develop automated and AI-assisted methods for diagnosing Mtb and TB pathology from digitised human lung tissue images. Some studies presented a completely automated method of diagnosis, while other studies developed AI-assisted diagnostic methods. Low-level focus areas included the development of a novel μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT scanner for soft tissue image contract, and use of multiresolution computed tomography to analyse the 3D structure of the human lung. High-level focus areas included the investigation the effects of aging on the number and size of small airways in the lungs using CT and whole lung high-resolution μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT, and the 3D microanatomy characterisation of human tuberculosis lung using μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT in conjunction with histology and immunohistochemistry. Additionally, a novel method for acquiring high-resolution 3D images of human lung structure and topology is also presented.ConclusionThe literature indicates that post 1950s, TB was predominantly studied using animal models even though no animal model reflects the full spectrum of human pulmonary TB disease and does not reproducibly transmit Mtb infection to other animals (Hunter, 2011). This explains why there are very few studies that used human lung tissue for detection or analysis of Mtb. Nonetheless, we found 10 studies that used human tissues (predominately lung) of which five studies proposed machine learning (ML) models for the detection of bacilli and the other five used CT on human lung tissue scanned ex-vivo.

Tuberculosis and increased incidence of cardiovascular disease: Cohort study using US and UK health records.

Limited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for pre-existing CVD risk. We carried out a cohort study using two separate datasets, estimating CVD incidence in people with TB versus those without. Using data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020 we matched adults with incident TB disease and no CVD history 2-years before TB diagnosis (US n=2,121; UK n=15,820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2-years before TB diagnosis and for 2-years subsequently. The acute period was defined as 3-months before/after TB diagnosis. TB, CVD and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios (IRR) for CVD events in people with TB compared to those without. CVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: IRRs were US 3.5 (95% Confidence Interval 2.7-4.4), UK 2.7 (2.2-3.3). Rate Ratios remained high after adjusting for differences in pre-existing CVD risk: US 3.2 (2.2-4.4), UK 1.6 (1.2-2.1). Increased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in pre-existing risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB.

Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life: a South African birth cohort study

Paediatric tuberculosis leads to more than 200 000 deaths annually. We aimed to investigate the incidence of Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life in the Drakenstein Child Health Study (DCHS), a South African cohort in a community with high tuberculosis and HIV incidence. In this prospective birth cohort study, we enrolled pregnant women aged 18 years or older who were between 20 and 28 weeks' of gestation in a peri-urban setting outside of Cape Town, South Africa. We followed up their children for tuberculosis until age 10 years. To measure M tuberculosis infection tuberculin skin tests were administered to children at age 6 months, 12 months, and then annually in children with a negative test, and at the time of a lower respiratory tract infection. Tuberculin skin test conversion was defined by an induration reaction of 10 mm or more. To measure tuberculosis disease, active surveillance was done throughout follow-up. Each episode of presumed tuberculosis disease was investigated using sputum induction, tested with Xpert MTB/RIF and liquid culture for M tuberculosis. Survival analyses were performed and multivariable Cox regression was used to measure factors associated with M tuberculosis infection or disease. Between March 5, 2012, and March 31, 2015, 1137 women and their 1143 children (248 [21·7%] of 1143 children were HIV-exposed, two [0·2%] children with HIV) were included in the analysis. Children were followed up for 8870 person-years (median follow-up 9·1 years [IQR 8·2-10·2]). The annual risk of tuberculin conversion during follow-up was 6·6 infections per 100 person-years (95% CI 5·8-7·3) but ranged from 4-9 infections per 100 person-years over the follow-up period. 98 children developed tuberculosis (1105 cases per 100 000 person-years; 95% CI 906-1347). The cumulative hazard of tuberculin conversion was 36% (95% CI 32-41) at age 8 years and the cumulative hazard of tuberculosis disease was 10% (8-12) at age 10 years. Preventive treatment was associated with a reduction in tuberculosis disease among children who had tuberculin conversion (adjusted hazard ratio 0·23 [95% CI 0·12-0·47]). Most cases of tuberculosis disease (78 [79%; 95% CI 69-86] of 98 children) occurred among children who had tuberculin skin test conversion but were not administered preventive treatment. In this prospective South African birth cohort, M tuberculosis transmission was consistently high throughout the first decade of life leading to approximately 10% of children developing tuberculosis disease. A multipronged approach to decrease paediatric tuberculosis is needed that combines preventive treatment for children at risk, reducing community M tuberculosis transmission, and active case finding. Bill & Melinda Gates Foundation, Medical Research Council South Africa, and National Research Foundation South Africa.

Burden and challenges in managing TB infection among people with occupational exposure to silica in India.

Occupational exposure to silica increases the risk of TB infection (TBI) and disease. This study aimed to determine the prevalence of TBI and explore challenges in TBI management in such individuals in two districts of India during 2023. This was an explanatory mixed-methods study with a quantitative cohort design and qualitative descriptive in-depth interviews. Among 1,555 individuals with occupational exposure to silica, 593 (38%, 95% CI 36-41) underwent interferon-gamma release assay (IGRA) for TBI, of whom 255 (43%, 95% CI 39-47) were found IGRA-positive. Males with occupational silica exposure for ≥20 years had a significantly higher risk of TBI. Of these 160 individuals eligible for TB preventive therapy (TPT), 153 (96%, 95% CI 92-98) were initiated on TPT and 124 (81%, 95% CI 74-88) completed TPT. The low uptake of IGRA was attributed to the stigma associated with TB and reluctance to undergo any medical evaluation. Compared to the general population, individuals with occupational exposure to silica have an almost two times higher prevalence of TBI. Further research is required to identify the threshold of silica exposure to be considered for screening for TBI. Efforts to increase awareness and decrease stigma can improve the uptake of testing for TBI and TB disease.

REFINING THE DEFINITION OF MILIARY/DISSEMINATED TUBERCULOSIS IN CANADA

While a multi-site definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein we sought to generate that evidence. We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively-diagnosed TB patients in Canada. Definitions were combined in a multi-variable logistic regression to determine risk factors for TB-related death in DTB. We applied two mutually exclusive definitions of DTB to our dataset: 1. 'strict' - TB disease associated with a positive TB culture in blood/bone marrow or TB disease associated with a miliary pattern on chest imaging and a positive TB culture or, 2. 'multisite' - TB disease in two or more non-contiguous sites. Among 2877 notified TB patients, 110 (3.8%) met the 'strict' definition, while 168 (5.8%) met the 'multisite' definition. Of all 278 DTB patients only 135 (48.6%) were notified as DTB using International Classification of Disease codes, and only 66 (23.7%) were classified as DTB by Canada's Public Health Agency. DTB patients, by either definition, were less likely to achieve cure/treatment completion and more likely to die. Risk factors for a fatal outcome included extremes of age, Canadian birth, central nervous system involvement, and HIV co-infection. Our findings support the combination of both a strict and multisite definition of DTB for purposes of reporting consistency and investigational comparability.

The impact of screening for tuberculosis exposure in the household in children with tuberculosis disease: A difficult riddle to solve.

Tuberculosis (TB) infection is transmitted by sharing the same airway with people with active TB. Children are often not considered the source of TB bacilli, and index case investigation is carried out after diagnosis. Here, we describe the impact of the presence of a household index case on childhood TB disease. The data of patients aged between 1 month and 18 years who were diagnosed with TB were collected. We compared patients according to whether they had an index case in the household or not. A total of 202 TB patients were enrolled, of whom 62 (30.7%) had a household index case. There was no significant difference in having a household index case between TB patients under the age of five (23.3%) and older children (33.8%) (p = .140). Pulmonary TB was present in 61.4% of the cases, and extrapulmonary TB was present in 38.6% of the cases. The rate of patients who had a household index case was significantly higher in pulmonary TB (46.8%) compared to extrapulmonary TB (5.1%) (p < .001). Pulmonary TB patients with a history of household contact were more likely to have diagnostic radiological findings (93.1%) compared to those without (75.8%) (p = .009). However, pulmonary TB patients without household contact history had a higher rate of diagnostic microbiological findings (59.1%) and constitutional symptoms (63.6%) (p = .019 and p = .013, respectively). Household contact research is an important epidemiological tool. However, considering the contact rates in the household, new and more comprehensive public health programs are required to prevent the spread of childhood tuberculosis.

Approaches and processes for paediatric chest X-ray classification used in the SHINE TB treatment-shortening trial.

<sec><title>INTRODUCTION</title>SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.</sec><sec><title>METHODS</title>Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.</sec><sec><title>RESULTS</title>A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.</sec><sec><title>DISCUSSION</title>Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research.</sec>.

Reasons for acceptance or nonparticipation in iAdhere: a trial of latent TB infection treatment.

<sec><title>BACKGROUND</title>Understanding the motivations behind clinical trial participation can help enhance recruitment strategies and determine the generalizability of trial results. This study focuses on the reasons for participating in or declining the Tuberculosis Trials Consortium Study 33 (iAdhere), a clinical trial on the treatment of latent tuberculosis infection (LTBI).</sec><sec><title>METHODS</title>A quantitative evaluation was conducted among screened patients to ascertain their reasons for participating or not in the iAdhere trial. The study gathered data from enrolled participants and those who chose not to enroll.</sec><sec><title>RESULTS</title>Among 1,002 enrolled individuals, 290 participants provided 749 reasons for enrolling. The most common reasons included access to shorter treatment regimens (56%), avoiding progression to TB disease (45%), and improving health (21%). Of the 670 eligible persons who chose not to enroll, 551 individuals provided 800 reasons, with the most common being a preference for standard therapy (17%), disinterest in study medication or TB therapy (both 13%), and the inconvenience of daily observed treatment (12%).</sec><sec><title>CONCLUSION</title>The desire for shorter treatment options and preventing active disease motivates participation in LTBI trials. The diverse reasons for declining enrolment suggest the importance of developing targeted recruitment strategies. These findings support exploring shorter treatment regimens and can guide future recruitment efforts.</sec>.

ANALYSIS OF QUALITY OF LIFE AND COMPLIANCE LEVEL OF PULMONARY TB PATIENTS AND BODY MASS INDEX IN POST-TRANSFERENCE TREATMENT ANTI TUBERCULOSIS IN HOSPITAL dr. M HAULUSSY AMBON

Tuberculosis is the most common multi-systemic infection, with various types of manifestation and clinical description, lung is the most common location for developing tuberculosis disease (WHO, 2018). As many as 58% of cases of pulmonary TB occur in 3 (three) countries such as Southeast Asia. Based on profile Service Health Maluku Province, in 2021 number of invention Pulmonary TB cases Service Health (Health Office) of Maluku Province to end in 2019 it reached 6,379 people or by 0.35 percent of total population in the province the largest as 1.8 million people.This research uses a quantitative observational design with a cross sectional approach. With sample use systematic type Purposive sampling of 83 respondents. Data analysis using linear regression. Results test statistics show the most influential variable to level pulmonary tuberculosis treatment is a level indicator compliance with level significance sig 0.000. Based on the results of the Multiple Linear Regression analysis, it shows that with a p-value of 0.00 0 &lt; 0.05, H 1 is accepted, so it is concluded that there is a simultaneous influence quality of life as well as the level of compliance of TB lung sufferers And body mass index on post treatment tb lung at DR M Haulussy Ambon Regional Hospital.

Risk of tuberculosis disease in Patients Receiving TNF-α Antagonist Therapy: A Meta-analysis of Randomized Controlled Trials

Risk of tuberculosis disease in Patients Receiving TNF-α Antagonist Therapy: A Meta-analysis of Randomized Controlled Trials