Risk of tuberculosis after achieving HIV virological suppression on antiretroviral therapy: a Danish nationwide prospective cohort study.

BACKGROUND: In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. METHODS: In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). RESULTS: Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). CONCLUSIONS: The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

Sequencing by binding rivals SMOR error-corrected sequencing by synthesis technology for accurate detection and quantification of minor (< 0.1%) subpopulation variants.

BACKGROUND: Detecting very minor (< 1%) subpopulations using next-generation sequencing is a critical need for multiple applications, including the detection of drug resistant pathogens and somatic variant detection in oncology. A recently available sequencing approach termed 'sequencing by binding (SBB)' claims to have higher base calling accuracy data "out of the box." This paper evaluates the utility of using SBB for the detection of ultra-rare drug resistant subpopulations in Mycobacterium tuberculosis (Mtb) using a targeted amplicon assay and compares the performance of SBB to single molecule overlapping reads (SMOR) error corrected sequencing by synthesis (SBS) data. RESULTS: SBS displayed an elevated error rate when compared to SMOR error-corrected SBS and SBB techniques. SMOR error-corrected SBS and SBB technologies performed similarly within the linear range studies and error rate studies. CONCLUSIONS: With lower sequencing error rates within SBB sequencing, this technique looks promising for both targeted and unbiased whole genome sequencing, leading to the identification of minor (< 1%) subpopulations without the need for error correction methods.

Risk factors associated with influenza A (H1N1)pdm09: a nested case control study of TB patients with ILI in Lahore District, Pakistan.

BACKGROUND: Co-morbidity with respiratory viruses including influenza A, cause varying degree of morbidity especially in TB patients compared to general population. This study estimates the risk factors associated with influenza A (H1N1)pdm09 in TB patients with ILI. METHODS: A cohort of tuberculosis (TB) patients who were admitted to and enrolled in a TB Directly Observed Therapy Program (DOTs) in tertiary care hospitals of Lahore (Mayo Hospital and Infectious Disease Hospital) were followed for 12 weeks. At the start of study period, to record influenza-like illness (ILI), a symptom card was provided to all the participants. Every participant was contacted once a week, in person. When the symptoms were reported by the participant, a throat swab was taken for the detection of influenza A (H1N1)pdm09. A nested case control study was conducted and TB patients with ILI diagnosed with influenza A (H1N1)pdm09 by conventional RT-PCR were selected as cases, while those who tested negative by conventional RT-PCR were enrolled as controls. All cases and controls in the study were interviewed face-to-face in the local language. Epidemiological data about potential risk factors were collected on a predesigned questionnaire. Logistic analysis was conducted to identify associated risk factors in TB patients with ILI. RESULTS: From the main cohort of TB patients (n = 152) who were followed during the study period, 59 (39%) developed ILI symptoms; of them, 39 tested positive for influenza A (H1N1)pdm09, while 20 were detected negative for influenza A (H1N1)pdm09. In univariable analysis, four factors were identified as risk factors (p < 0.05). The final multivariable model identified one risk factor (sharing of towels, P = 0.008)) and one protective factor (wearing a face mask, p = < 0.001)) for influenza A (H1N1)pdm09 infection. CONCLUSION: The current study identified the risk factors of influenza A (H1N1)pdm09 infection among TB patients with ILI.

Diagnostic accuracy of the Xpert® MTB/XDR assay for detection of Isoniazid and second-line antituberculosis drugs resistance at central TB reference laboratory in Tanzania.

INTRODUCTION: Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. METHODS: We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. FINDINGS: We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4-96.7); for Isoniazid, 96.6 (95% CI, 92.1-98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8-99.7); for Amikacin, 96.6%; and (95% CI 92.1-98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. CONCLUSION: The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Real-time evaluation of a multi-agency TB-screening event for persons experiencing homelessness in a town with a low incidence of TB in England.

Real-time evaluation (RTE) supports populations (e.g., persons experiencing homelessness (PEH) to engage in evaluation of health interventions who may otherwise be overlooked. The aim of this RTE was to explore the understanding of TB amongst PEH, identify barriers/facilitators to attending screening for PEH alongside suggestions for improving TB-screening events targeting PEH, who have high and complex health needs. This RTE composed of free-text structured one-to-one interviews performed immediately after screening at a single tuberculosis (TB) screening event. Handwritten forms were transcribed for thematic analysis, with codes ascribed to answers that were developed into core themes. All RTE participants (n=15) learned about the screening event on the day it was held. Key concerns amongst screening attendees included: stigma around drug use, not understanding the purpose of TB screening, lack of trusted individuals/services present, too many partner organizations involved, and language barriers. Facilitators to screening included a positive welcome to the event, a satisfactory explanation of screening tests, and sharing of results. A need for improved event promotion alongside communication of the purpose of TB screening amongst PEH was also identified. A lack of trust identified by some participants suggests the range of services present should be reconsidered for future screening events.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Enhancing multi-class lung disease classification in chest x-ray images: A hybrid manta-ray foraging volcano eruption algorithm boosted multilayer perceptron neural network approach.

One of the most used diagnostic imaging techniques for identifying a variety of lung and bone-related conditions is the chest X-ray. Recent developments in deep learning have demonstrated several successful cases of illness diagnosis from chest X-rays. However, issues of stability and class imbalance still need to be resolved. Hence in this manuscript, multi-class lung disease classification in chest x-ray images using a hybrid manta-ray foraging volcano eruption algorithm boosted multilayer perceptron neural network approach is proposed (MPNN-Hyb-MRF-VEA). Initially, the input chest X-ray images are taken from the Covid-Chest X-ray dataset. Anisotropic diffusion Kuwahara filtering (ADKF) is used to enhance the quality of these images and lower noise. To capture significant discriminative features, the Term frequency-inverse document frequency (TF-IDF) based feature extraction method is utilized in this case. The Multilayer Perceptron Neural Network (MPNN) serves as the classification model for multi-class lung disorders classification as COVID-19, pneumonia, tuberculosis (TB), and normal. A Hybrid Manta-Ray Foraging and Volcano Eruption Algorithm (Hyb-MRF-VEA) is introduced to further optimize and fine-tune the MPNN's parameters. The Python platform is used to accurately evaluate the proposed methodology. The performance of the proposed method provides 23.21%, 12.09%, and 5.66% higher accuracy compared with existing methods like NFM, SVM, and CNN respectively.

Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study.

BACKGROUND AND OBJECTIVE: Pyrazinamide (PZA) is the standard first-line treatment for tuberculosis (TB); however, its safety in elderly patients has not been thoroughly investigated. METHODS: This retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for TB between July 2010 and March 2022. Patients were categorized into HRE (isoniazid, rifampicin and ethambutol) and HREZ (isoniazid, rifampicin, ethambutol and PZA) groups. Primary outcomes included in-hospital mortality and overall adverse events (characterized by a composite of hepatotoxicity, gout attack, allergic reactions and gastrointestinal intolerance). Secondary outcomes included the length of hospital stay, 90-day readmission and use of drugs related to the primary outcome adverse events. Data were analysed using propensity score matching; we also conducted a subgroup analysis for those aged ≥75 years. RESULTS: Among 19,930 eligible patients, 8924 received HRE and 11,006 received HREZ. Propensity score matching created 3578 matched pairs with a mean age of approximately 80 years. Compared with the HRE group, the HREZ group demonstrated a higher proportion of overall adverse events (3.1% vs. 4.7%; p < 0.001), allergic reactions (1.4% vs. 2.5%; p < 0.001) and antihistamine use (21.9% vs. 27.6%; p < 0.001). No significant differences were observed regarding in-hospital mortality, hepatotoxicity or length of hospital stay between the groups. Subgroup analysis for those aged ≥75 years showed consistent results. CONCLUSION: Medical practitioners may consider adding PZA to an initial treatment regimen even in elderly patients with TB.

Key recent advances in TB vaccine development and understanding of protective immune responses against Mycobacterium tuberculosis.

Tuberculosis is the leading infectious disease killer globally due to a single pathogen. Despite wide deployment of standard drug regimens, modern diagnostics and a vaccine (bacille Calmette Guerin, BCG), the global tuberculosis epidemic is inadequately controlled. Novel, effective vaccine(s) are a crucial element of the World Health Organization End TB Strategy. TB vaccine research and development has recently been catalysed by several factors, including a revised strategy focused first on preventing pulmonary TB in adolescents and adults who are the main source of transmission, and encouraging evaluations of novel efficacy endpoints. Renewed enthusiasm for TB vaccine research has also been stimulated by recent preclinical and clinical advancements. These include new insights into underlying protective immune responses, including potential roles for 'trained' innate immunity and Th1/Th17 CD4+ (and CD8+) T cells. The field has been further reinvigorated by two positive proof of concept efficacy trials: one evaluating a potential new use of BCG in preventing high risk populations from sustained Mycobacterium tuberculosis infection and the second evaluating a novel, adjuvanted, recombinant protein vaccine candidate (M72/AS01E) for prevention of disease in adults already infected. Fourteen additional candidates are currently in various phases of clinical evaluation and multiple approaches to next generation vaccines are in discovery and preclinical development. The two positive efficacy trials and recent studies in nonhuman primates have enabled the first opportunities to discover candidate vaccine-induced correlates of protection, an effort being undertaken by a broad research consortium.

Improving the diagnosis of active tuberculosis: a novel approach using magnetic particle-based chemiluminescence LAM assay.

OBJECTIVES: Tuberculosis (TB) is a significant global health concern, given its high rates of morbidity and mortality. The diagnosis using urine lipoarabinomannan (LAM) primarily benefits HIV co-infected TB patients with low CD4 counts. The focus of this study was to develop an ultra-sensitive LAM assay intended for diagnosing tuberculosis across a wider spectrum of TB patients. DESIGN & METHODS: To heighten the sensitivity of the LAM assay, we employed high-affinity rabbit monoclonal antibodies and selected a highly sensitive chemiluminescence LAM assay (CLIA-LAM) for development. The clinical diagnostic criteria for active TB (ATB) were used as a control. A two-step sample collection process was implemented, with the cutoff determined initially through a ROC curve. Subsequently, additional clinical samples were utilized for the validation of the assay. RESULTS: In the assay validation phase, a total of 87 confirmed active TB patients, 19 latent TB infection (LTBI) patients, and 104 healthy control samples were included. Applying a cutoff of 1.043 (pg/mL), the CLIA-LAM assay demonstrated a sensitivity of 55.2% [95%CI (44.13%~65.85%)], and a specificity of 100% [95%CI (96.52%~100.00%)], validated against clinical diagnostic results using the Mann-Whitney U test. Among 11 hematogenous disseminated TB patients, the positive rate was 81.8%. Importantly, the CLIA-LAM assay consistently yielded negative results in the 19 LTBI patients. CONCLUSION: Overall, the combination of high-affinity antibodies and the CLIA method significantly improved the sensitivity and specificity of the LAM assay. It can be used for the diagnosis of active TB, particularly hematogenous disseminated TB.

Tuberculosis in Poland in 2021. / Gruzlica w Polsce w 2021 r.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2021 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2021, data from Statistics Poland on deaths from tuberculosis in 2020, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2021 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2021, 3704 TB cases were reported in Poland. The incidence rate was 9.7 cases per 100,000 with large variability between voivodeships from 5.4 to 12.6 per 100,000. A decrease in the incidence with respect to 2020 was found in 8 voivodeships, the most significant in lubuskie voivodship (42.6%). The number of all pulmonary tuberculosis cases was 3,553 i.e. 9.3 per 100,000. Pulmonary cases represented 95.9% of all TB cases. In 2021, 151 extrapulmonary TB cases were notified (4.1% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,970 cases (83.6% of all pulmonary TB cases, the incidence rate 7.8 per 100,000). The number of smear-positive pulmonary TB cases was 2,085 i.e. 5.5 per 100,000 (58.7% of all pulmonary TB cases). In 2021, there were 54 cases (25 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.9% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with the age group from 0.6 per 100,000 among children (0-14 years) to 15.8 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 11.7 per 100,000. There were 37 cases in children up to 14 years of age (1.0% of the total) and 51 cases in adolescents between 15 and 19 years of age - rates 0.6 and 2.8 per 100,000 respectively. In 2021, there were 2,690 cases of tuberculosis in men and 1,014 in women. The TB incidence in men - 14.6 per 100,000 was almost 3.0 times higher than among women - 5.1. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 55-59 years, 30.5 vs. 6.6 and in age group 60 to 64 years, 26.0 vs. 5.7. In 2021, there were 132 patients of foreign origin among all cases of tuberculosis in Poland (3.6%). In 2020, TB was the cause of death for 474 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: The incidence of tuberculosis in Poland in 2021 was 10.2% higher than in 2020. The percentage of tuberculosis cases with bacteriological confirmation was 82.6%, higher than the average in EU/EEA countries (72.0%). The percentage of MDR-TB cases was lower than the average in EU/EEA countries (1.9% vs. 3.8%). The highest incidence rates are found in Poland in the older age groups (in EU/EEA countries in people aged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.0%, the average in the EU/EEA countries was 3.5%. The incidence of tuberculosis in men was nearly three times higher than in women in Poland. The impact of migration on the epidemiological situation of tuberculosis in Poland in 2021 was smaller than in the EU/EEA countries (in Poland, the percentage of foreigners among all TB patients was 3.6 vs. 33.8% in the EU/EEA).

The immunogenetics of tuberculosis (TB) susceptibility.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death due to a single bacterial agent, with approximately 10.6 million people developing active disease and 1.6 million deaths reported globally in 2021. After exposure, some, but not all individuals, will become infected with the bacillus. However, only a small fraction (approximately 5 to 15%) of these individuals will progress to clinical disease, while in the remainder, infection is seemingly contained, and no signs of clinical disease are shown. Numerous observations have advocated for the role of host genetics in the display of these inter-individual variabilities in infection and disease phenotypes. In this review, we will provide an overview of the approaches, findings and limitations of the very first studies investigating TB genetic susceptibility to more recent studies. Lastly, we highlight several approaches, namely, linkage analyses and association studies, proposed to discover genetic markers associated with TB susceptibility. This review also explored the concept of polygenic risk scores (PRS) for prediction of tuberculosis susceptibility. The identification of host genetic factors influencing TB susceptibility/resistance is paramount to not only better understand the physiopathology of the disease but also explore more effective approaches for the development of both optimal preventive measures (i.e. better vaccines) and treatments of TB disease.

Incidence of pulmonary tuberculosis in suburban Bissau, Guinea-Bissau between 2004 and 2020: a prospective cohort study.

OBJECTIVES: Previous studies have found declining incidence of tuberculosis (TB) in Bissau, Guinea-Bissau. This study aimed to report incidence rates of TB for the period 2004-2020, stratifying by sex, smear-status, and HIV-status, as well as describe developments in TB case fatality rate and diagnostic delay. DESIGN AND METHODS: Data from the Bandim Health Project HDSS and the TB registry from Jan 1st, 2004 to Dec 31st, 2020 were used. Incidence rates were calculated for each year and for smear-positive, smear-negative, HIV-positive, HIV-negative, and unknown HIV-status. Incidence rate ratio and test for trend were done using a one-step Newton approximation to the log-linear Poisson regression coefficient. RESULTS: Overall TB incidence declined only slightly over the period from 294 per 100,000 in 2004 to 273 in 2020. TB/HIV coinfection declined from 108 in 2004 to 14 in 2020, as did incidence among females and smear-negative cases. CONCLUSIONS: Incidence of PTB in Bissau, Guinea-Bissau is declining slowly, if at all. TB incidence among females, smear-negative TB, TB case fatality rate, and TB/HIV coinfection and diagnostic delay are declining.

Comparing Mycobacterium tuberculosis transmission reconstruction models from whole genome sequence data.

Genomic epidemiology is routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools exist that reconstruct transmission networks by coupling genomic data with epidemiological models. Resulting inferences can improve our understanding of pathogen transmission dynamics, and yet the performance of these tools has not been evaluated for tuberculosis (TB), a disease process with complex epidemiology including variable latency and within-host heterogeneity. Here, we performed a systematic comparison of six publicly available transmission reconstruction models, evaluating their accuracy when predicting transmission events in simulated and real-world Mycobacterium tuberculosis outbreaks. We observed variability in the number of transmission links that were predicted with high probability (P ≥ 0.5) and low accuracy of these predictions against known transmission in simulated outbreaks. We also found a low proportion of epidemiologically supported case-contact pairs were identified in our real-world TB clusters. The specificity of all models was high, and a relatively high proportion of the total transmission events predicted by some models were true links, notably with TransPhylo, Outbreaker2, and Phybreak. Our findings may inform the choice of tools in TB transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.

Characteristics and treatment outcomes of co-infected tuberculosis patients with human immunodeficiency virus in Southeast China, 2012-2021.

BACKGROUND: Tuberculosis (TB) is a chronic respiratory infection. Co-infection with human immunodeficiency virus (HIV) has been a significant obstacle to TB control. Insufficient attention has been given to TB/HIV, and more information is needed to address this issue. We conducted an observational study to investigate the epidemiological characteristics, treatment outcomes and its associated factors of HIV-positive TB patients in Southeast China. METHODS: An observational study was conducted based on data collected directly from China National TB Surveillance System during 2012-2021. Epidemiological characteristics, drug resistance and outcomes were described as frequency (n) and percentage (%). Risk factors for unsuccessful outcomes were determined using univariate (chi-squared) and multivariate logistic regression analysis. RESULTS: A total of 347 TB/HIV cases were included, and the proportion of HIV-positive cases among all TB cases increased significantly from 0.06% to 2012 to 0.40% in 2021. The majority of cases were males (86.5%), non-local household registers (139, 40.1%), farmers or workers (179, 51.6%), and aged 40-59 (142, 40.9%). Of 347 cases, 290 (83.6%) had pulmonary TB (PTB), 10 (2.9%) had extra pulmonary TB (EPTB) and 47(13.5%) had both PTB and EPTB. A total A total of 258 (74.4%) were HIV positive prior to TB diagnosis. 8.0% (4/50) of cases were resistant to rifampicin (RIF) and 274 patients (83.8%) had successful outcomes. Being non-local (AOR = 2.193, 95% CI = 1.196-4.022, P = 0.011) and diagnosed HIV infection after TB (AOR = 2.365, 95% CI = 1.263-4.430, P = 0.007) were independent risk factors for unsuccessful outcomes of anti-TB treatment. CONCLUSION: During 2012-2021, the proportion of HIV-positive cases among all TB cases increased significantly in Southeast China. HIV-positive TB patients were significantly more likely to develop resistance to RIF and INH and unsuccessful anti-TB treatment. Non-local registration and becoming HIV positive after TB diagnosis were independent risk factors associated with unsuccessful outcomes.

Simple and low-cost antibiotic susceptibility testing for Mycobacterium tuberculosis using screen-printed electrodes.

One quarter of the global population is thought to be latently infected by Mycobacterium tuberculosis (TB) with it estimated that 1 in 10 of those people will go on to develop active disease. Due to the fact that M. tuberculosis (TB) is a disease most often associated with low- and middle-income countries, it is critical that low-cost and easy-to-use technological solutions are developed, which can have a direct impact on diagnosis and prescribing practice for TB. One area where intervention could be particularly useful is antibiotic susceptibility testing (AST). This work presents a low-cost, simple-to-use AST sensor that can detect drug susceptibility on the basis of changing RNA abundance for the typically slow-growing M. tuberculosis (TB) pathogen in 96 h using screen-printed electrodes and standard molecular biology laboratory reactionware. In order to find out the sensitivity of applied sensor platform, a different concentration (108 -103  CFU/mL) of M. tuberculosis was performed, and limit of detection and limit of quantitation were calculated as 103.82 and 1011.59  CFU/mL, respectively. The results display that it was possible to detect TB sequences and distinguish antibiotic-treated cells from untreated cells with a label-free molecular detection. These findings pave the way for the development of a comprehensive, low-cost, and simple-to-use AST system for prescribing in TB and multidrug-resistant tuberculosis.

Community based peer-led TB screening intervention: an innovative approach to increase TB knowledge, presumptive case identification, and referral among sexual minority people in urban Bangladesh.

INTRODUCTION: One of the contributors to tuberculosis (TB) burden among vulnerable populations, such as sexual minority people, is the delay in case finding and notification. Given their socially excluded, hard-to-reach nature, community-led approaches need to be introduced to facilitate their screening of TB symptoms and their subsequent referral to TB healthcare providers. This article aimed to explore the existing challenges surrounding TB screening and referral, and the implementation facilitators and barriers of the proposed community-based TB screening model for sexual minority people in Dhaka, Bangladesh. METHODS: This study followed the quasi-experimental design using mixed methods (i.e., qualitative and quantitative) approach. The study participants who were also a part of the community-led TB screening model included sexual minority people enrolled in HIV prevention interventions. In addition to quantitative inquiry, in-depth interviews were conducted on sexual minority people, focus group discussions were also conducted on them and HIV prevention service providers, and key-informant interviews were conducted on service providers, programmatic experts and TB researchers. Data were analyzed using content, contextual and thematic approaches. RESULTS: The 'Six Steps in Quality Intervention Development' framework was used to guide the development of the community-based TB screening model. In Step 1 (identifying the problem), findings revealed low rates of TB screening among sexual minority people enrolled in the HIV prevention intervention. In Step 2 (identifying contextual factors for change), various individual, and programmatic factors were identified, which included low knowledge, low-risk perception, prioritization of HIV services over TB, and stigma and discrimination towards these populations. In Step 3 (deciding change mechanism), community-based screening approaches were applied, thus leading to Step 4 (delivery of change mechanism) which designed a community-based approach leveraging the peer educators of the HIV intervention. Step 5 (testing intervention) identified some barriers and ways forward for refining the intervention, such as home-based screening and use of social media. Step 6 (collecting evidence of effectiveness) revealed that the main strength was its ability to engage peer educators. CONCLUSION: This study indicates that a community-based peer-led TB screening approach could enhance TB screening, presumptive TB case finding and referral among these populations. Therefore, this study recommends that this approach should be incorporated to complement the existing TB program.

Design, synthesis, molecular docking, and biological evaluation of coumarin-thymidine analogs as potent anti-TB agents.

With the intent to discover new antituberculosis (TB) compounds, coumarin-thymidine analogs were synthesized using second-order nucleophilic substitution reactions of bromomethyl coumarin with thymidine. The newly synthesized coumarin-thymidine conjugates (1a-l) were characterized using IR, NMR, GC-MS, and CHN elemental analysis. The novel conjugates were found to exhibit potent anti-TB activity against the Mycobacterium tuberculosis H37 Rv strain, with minimum inhibitory concentrations (MIC) of the active compounds ranging between 0.012 and 0.482 µM. Compound 1k was established as the most active candidate with a MIC of 0.012 µM. The toxicity study on HEK cells confirmed the nontoxic nature of compounds 1e, 1h, 1i, 1j, and 1k. Also, the most active compounds (1k, 1j, and 1e) were stable in the pH range from 2.5 to 10, indicating compatibility with the biophysical environment. Based on the pKa studies, compounds 1k, 1j, and 1e are capable of crossing lipid-membrane barriers and acting on target cells. Molecular docking studies on the M. tuberculosis ß-oxidation trifunctional enzyme (PDB ID: 7O4V) were conducted to investigate the mechanisms of anti-TB activity. All compounds showed excellent hydrogen binding interactions and exceptional docking scores against M. tuberculosis, which was in accordance with the results. Compounds 1a-l possessed excellent affinity to proteins, with binding energies ranging from -7.4 to -8.7 kcal/mol.

Development and Validation of LC-MS/MS Method for the Determination of 1-Methyl-4-Nitrosopiperazine (MNP) in Multicomponent Products with Rifampicin-Analytical Challenges and Degradation Studies.

Rifampicin is an essential medicine for treating and preventing tuberculosis (TB). TB is a life-threatening infectious disease and its prevention and treatment are public health imperatives. In the time of a global crisis of nitrosamine contamination of medicinal products, patient safety and a reduction in the number of drug recalls at the same time are crucial. In this work, the LC-MS/MS method was developed for the determination of the 1-methyl-4-nitrosospiperazine (MNP), a genotoxic nitrosamine impurity in various products containing rifampicin at a 5.0 ppm limit level according to Food and Drug Administration (FDA). Extraction with neutralization was necessary due to the matrix and solvent effect associated with the complexity of the rifampicin product. The developed method was validated in accordance with regulatory guidelines. Specificity, accuracy, precision, limit of detection, and limit of quantification parameters were evaluated. The recovery of the MNP was 100.38 ± 3.24% and the intermediate precision was 2.52%. The contamination of MNP in Rifampicin originates in the manufacturing process of the drug. Furthermore, the results of the forced degradation experiments show that the formation of MNP is possible by two mechanisms: through degradation of rifampicin and the oxidation of 1-amino-4-methyl-piperazine. This article points out that it is necessary to monitor and describe degradation products and the mechanism of degradation of potentially affected active pharmaceutical ingredient (API) with respect to the formation of nitrosamines during stress testing, as it was done in the following work for rifampicin in multicomponent products.

[Tuberculosis remains a public health issue in South Africa]. / La tuberculose demeure un enjeu de santé publique en Afrique du Sud.

Tuberculosis is an airborne infectious disease that can damage the lungs and other body organs. Early detection of people infected with Koch's bacillus is important because tuberculosis is a contagious disease. It can be cured. It is still a very common disease in South Africa and is fatal for sixty thousand people per year. Tuberculosis remains a major health problem for which the public authorities must put in place more effective prevention and management policies, particularly by improving the training of nurses and doctors.