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Hybrid deep learning system combining radiological and clinical data for improved tuberculosis diagnosis 结合放射学和临床数据的混合深度学习系统,用于改进结核病诊断
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.11.006
Navnath B. Pokale , Anjali Shrivastav , Kanchan K. Doke , Bhavesh Kataria , Ritesh Shrivastav , Aparna Shirkande
Tuberculosis (TB) remains among the leading causes of infectious mortality. Diagnosis is challenging because imaging and clinical data must be interpreted in tandem. Chest X-rays and computed tomography scans provide screening but require expert readers, while clinical variables such as age, body mass index (BMI), symptoms, HIV status and socio-economic factors capture risk information absent from images. Appending clinical scores to radiologic outputs raised the area under the receiver-operating-characteristic curve from around 0.72–0.78 to 0.84, but conventional convolutional networks cannot fully model interactions between modalities. A vision transformer represents chest images as sequences of patch embeddings, while a tabular transformer process cleaned and normalized clinical variables. A cross-modal attention module enables the image tokens to attend to clinical tokens, and a contrastive pre-training objective encourages radiological and clinical representations from the same patient to align while separating those from different patients. In this paper, we propose a hybrid deep learning model, which jointly learns the chest imaging and structured clinical data using a cross-modal transformer with contrastive pre-training. The method jointly learns radiological-clinical representations in order to improve the accuracy and interpretability of the diagnosis. Evaluated on two open-access cohorts (TB Portals and Integrated Mycobacterial CT), the system attained an AUC of 0.96 and accuracy of 0.90 approximately 10 % more than CNN-based baselines. Attention and SHAP analyses showed that variables such as HIV status and low BMI direct the attention of the model to important areas of the lung. This combination of radiological and clinical data promotes better diagnostics and provides a viable pathway for TB diagnosis in resource limited settings.
结核病仍然是传染性死亡的主要原因之一。诊断是具有挑战性的,因为影像学和临床数据必须串联解释。胸部x光片和计算机断层扫描提供了筛查,但需要专业的读者,而年龄、身体质量指数(BMI)、症状、艾滋病毒状况和社会经济因素等临床变量捕捉了图像中缺乏的风险信息。将临床评分附加到放射学输出将接受者操作特征曲线下的面积从大约0.72-0.78提高到0.84,但传统的卷积网络不能完全模拟模式之间的相互作用。视觉转换器将胸部图像表示为贴片嵌入序列,而表格转换器处理清洗和规范化临床变量。跨模态注意模块使图像标记能够关注临床标记,对比的预训练目标鼓励来自同一患者的放射和临床表征保持一致,同时将来自不同患者的表征分开。在本文中,我们提出了一种混合深度学习模型,该模型使用具有对比预训练的跨模态转换器共同学习胸部成像和结构化临床数据。该方法联合学习影像学和临床表征,以提高诊断的准确性和可解释性。在两个开放获取队列(TB Portals和综合分枝杆菌CT)上进行评估,该系统的AUC为0.96,准确率为0.90,比基于cnn的基线高出约10%。注意力和SHAP分析表明,HIV状态和低BMI等变量将模型的注意力引向肺部的重要区域。这种放射学和临床数据的结合促进了更好的诊断,并为资源有限的情况下的结核病诊断提供了一条可行的途径。
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引用次数: 0
Predicting multi-drug resistant tuberculosis using machine learning on genomic and clinical data 利用基因组和临床数据的机器学习预测多重耐药结核病
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.11.013
Komal Saxena , S Shyni Carmel Mary , Prolay Ghosh , Chinnem Rama Mohan , Mohd Naved , Mukesh Madanan

Background

Tuberculosis (TB) is still the largest cause of death in the world, especially in countries with low and medium incomes. Multi-Drug Resistant Tuberculosis (MDR-TB), which is resistant to isoniazid and rifampicin, is a new type of tuberculosis that makes treatment and disease control much harder. Conventional diagnostic methods, like quantitative drug resistance tests and genetic tools, take a lot of time and resources, and they aren't always available in places with few resources. New developments in whole-genome sequencing and the availability of clinical data make it possible to use machine learning to quickly and accurately find MDR-TB.

Methods

This study uses genetic and clinical data from a freely available set of about 5000 TB patient samples, which includes cases that are drug-susceptible, MDR, and highly drug-resistant (XDR). We use feature selection and normalization methods to prepare whole-genome sequencing data and clinical factors. Logistic Regression, Random Forest, Support Vector Machine, Gradient Boosting Machine, and Deep Neural Networks are built and tested using stratified cross-validation. Metrics like accuracy, precision, recall, F1-score, and AUC-ROC are used to measure how well a model works.

Results

The results showed that the Gradient Boosting and Deep Neural Network models were the most accurate at predicting (92.3 % and 93.1 %, respectively) and had the best AUC-ROC scores (94.7 % and 95.4 %, respectively). It was also shown that these models were better at finding MDR-TB cases. While genomic data was introduced to clinical records, the version have become more strong and correct than while genomic statistics was used alone. Key genetic changes and clinical factors that have an effect on drug resistance were found through feature value studies.

Conclusion

Using genetic and clinical data in machine learning algorithms to detect MDR-TB is promising, fast, and accurate, especially in low-resource areas. Future research should incorporate more data kinds, simplify models, and expand datasets to increase diagnostic accuracy and practicality.
背景结核病仍然是世界上最大的死亡原因,特别是在低收入和中等收入国家。耐多药结核病(MDR-TB)对异烟肼和利福平具有耐药性,是一种新型结核病,使治疗和疾病控制变得更加困难。传统的诊断方法,如定量耐药性测试和基因工具,需要花费大量的时间和资源,而且在资源匮乏的地方并不总是可用的。全基因组测序的新发展和临床数据的可用性使得利用机器学习快速准确地发现耐多药结核病成为可能。方法本研究使用了一组免费提供的约5000例结核病患者样本的遗传和临床数据,其中包括药物敏感、耐多药和高度耐药(XDR)病例。我们使用特征选择和归一化方法来准备全基因组测序数据和临床因素。逻辑回归,随机森林,支持向量机,梯度增强机和深度神经网络的建立和测试使用分层交叉验证。准确度、精度、召回率、f1分数和AUC-ROC等指标用于衡量模型的工作效果。结果梯度增强模型和深度神经网络模型预测准确率最高(分别为92.3%和93.1%),AUC-ROC评分最高(分别为94.7%和95.4%)。研究还表明,这些模型更善于发现耐多药结核病病例。当基因组数据被引入临床记录时,其版本比单独使用基因组统计时变得更加强大和正确。通过特征值研究发现影响耐药的关键遗传变化和临床因素。结论在机器学习算法中使用遗传和临床数据检测耐多药结核病是一种有前景的、快速和准确的方法,特别是在资源匮乏的地区。未来的研究应纳入更多的数据类型,简化模型,扩大数据集,以提高诊断的准确性和实用性。
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引用次数: 0
Comparative assessment of cartridge based nucleic acid amplification technique (CBNAAT) with gold standard LJ culture and smear microscopy in diagnosis of pulmonary and extra pulmonary tuberculosis in Tripura 盒式核酸扩增技术(CBNAAT)与金标准LJ培养和涂片镜检诊断特里普拉邦肺结核和肺外肺结核的比较评价
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.05.005
Debosmita Paul , Pradip Kr Das , Niladri Sekhar Das , Gourab Chakraborty , Aparna Paul

Background

The hope of tuberculosis elimination by 2025 has been put in a global dilemma by the emergence of Multidrug Resistant Tuberculosis (MDR-TB). Furthermore, the disparity between smear examination and CBNAAT in low resource settings can hamper the elimination drive in developing nations where infrastructure for culture methods is limited. In this study we compared the results of CBNAAT and smear examination with that of solid culture as the gold standard.

Methods

A total of 184 pulmonary and extra-pulmonary clinical samples were included in this study. These were then subjected to Ziehl Neelson staining, CBNAAT and solid culture in LJ media. Sensitivity, specificity, Positive Predictive Values and Negative Predictive Values were calculated for bacilloscopy and CBNAAT in comparison to gold standard culture.

Result

The overall sensitivity was higher for CBNAAT (97.29 %) but smear microscopy showed higher specificity (92.5 %). PPV and NPV of smear microscopy was 75 % and 97.14 % and for CBNAAT was 55.42 %, and 99.10 % respectively. Sensitivity of culture and smear microscopy done conjointly showed a high sensitivity of 96.97 %. CBNAAT also detected 9 culture and smear negative samples as positive.

Conclusion

Diagnostic efficacy of CBNAAT or the Cepheid GeneXpert assay as a screening method for tuberculosis was significantly higher than smear microscopy. However, used conjointly, the scope of differentiating MTB, NTM and RIF resistant TB is expanded. Nevertheless, the need for an accurate on-site technology for the simultaneous identification of NTM and MTB is indubitable at this stage.
到2025年消除结核病的希望由于耐多药结核病(MDR-TB)的出现而陷入全球困境。此外,在资源匮乏的环境下,涂片检查和CBNAAT之间的差异可能会阻碍发展中国家的消除动力,因为发展中国家的培养方法基础设施有限。在本研究中,我们将CBNAAT和涂片检查结果与固体培养结果作为金标准进行了比较。方法本研究共纳入184例肺及肺外临床标本。然后进行Ziehl - Neelson染色,CBNAAT和LJ培养基固体培养。计算bacilloscopy和CBNAAT与金标准培养相比的敏感性、特异性、阳性预测值和阴性预测值。结果CBNAAT的总灵敏度为97.29%,而涂片镜检的特异性为92.5%。涂片镜检的PPV和NPV分别为75%和97.14%,CBNAAT的PPV和NPV分别为55.42%和99.10%。培养和涂片镜检的灵敏度为96.97%。CBNAAT还检测出9份培养和涂片阴性样本为阳性。结论CBNAAT或造父变星GeneXpert检测对结核病的诊断效果明显高于涂片镜检。然而,如果联合使用,则扩大了MTB, NTM和RIF耐药结核病的区分范围。然而,在这个阶段,需要一种准确的现场技术来同时识别NTM和MTB是毋庸置疑的。
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引用次数: 0
An observational study on the utilization of cartridge based nucleic acid amplification test (CBNAAT) in diagnostic evaluation of chronic ulcer with respect to histopathological examination 基于盒型核酸扩增试验(CBNAAT)在慢性溃疡组织病理学诊断评价中的应用观察研究
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.05.007
Priyanka Lakhotiya , Ummed Singh Parihar , Kalpana Agarwal , Rajveer Kuldeep , Ramakant Dixit , Pramod Rawal , Hans Raj

Introduction

An ulcer is defined as a discontinuity of either skin or mucous membrane due to loss of blood supply. Chronic non healing ulcers may required 6 weeks or more to heal after coventional therapies. Objective: To compare the diagnostic evaluation of chronic ulcer by CBNAAT and histopathology examination.

Methods

Prospective Observational study conducted on 100 cases of chronic non-healing ulcer by consecutive sampling attended to outdoor and indoor patient department of surgery for one year period (July 2021–august 2022) at JLN Hospital, Ajmer.

Results

Mean age was 44.73 ± 16.34 years with age range of 12–80 years. Male: Female ratio was found to be 1.5:1. Out of 100 cases, tuberculosis was diagnosed in 14% cases by CBNAAT and in 13% cases by histopathological examination. Out of 14 CBNAAT positive cases, 28.57% cases were found to be rifampicin resistant. For CBNAAT, sensitivity is 64.28% and specificity is 95.34%. So Positive predictive value is 69.23% and negative predictive value is 94.25%.

Conclusion

In chronic wounds, CBNAAT had high specificity and low sensitivity, making it a diagnostic tool.
溃疡的定义是由于血液供应不足引起的皮肤或粘膜的不连续性。慢性不愈合溃疡在常规治疗后可能需要6周或更长时间才能愈合。目的:比较CBNAAT与组织病理学检查对慢性溃疡的诊断价值。方法采用连续抽样的方法,对100例慢性不愈合性溃疡患者(2021年7月- 2022年8月)在Ajmer市JLN医院室外和室内外科就诊1年。结果患者平均年龄44.73±16.34岁,年龄范围12 ~ 80岁。男女比例为1.5:1。在100例病例中,14%的病例通过CBNAAT诊断为结核病,13%的病例通过组织病理学检查诊断为结核病。14例CBNAAT阳性病例中,利福平耐药病例占28.57%。CBNAAT的敏感性为64.28%,特异性为95.34%。阳性预测值为69.23%,阴性预测值为94.25%。结论CBNAAT在慢性伤口诊断中具有高特异性和低敏感性,可作为一种诊断工具。
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引用次数: 0
Limitations in current tuberculosis diagnostics and the path to the future 当前结核病诊断的局限性和未来之路
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.10.001
V.K. Arora (Chairman) , Sanjay Rajpal , Ankita Anand
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引用次数: 0
Direct targeted next-generation sequencing for diagnosis of drug-resistant tuberculosis from clinical samples – An update 用于从临床样本中诊断耐药结核病的直接靶向新一代测序-最新进展
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.02.019
Radha Gopalaswamy , Bhargavi Subramanian , Manisha Parthasarathy , Chandrasekaran Padmapriyadarsini , Sivakumar Shanmugam
Timely detection of drug resistance is a pre-requisite to tuberculosis management globally. While phenotypic drug susceptibility testing (pDST) by liquid or solid method takes time, current genotypic DST assays can be performed directly from clinical specimens but target only a limited number of resistance variants. Targeted Next Generation Sequencing (tNGS) is a rapid, cost-effective method using direct sample to perform the sequencing than compared to whole genome sequencing (WGS) which requires culture. tNGS provides comprehensive drug resistance profiling with turnaround time of 3–4 days when done directly from clinical samples. For respiratory samples with rifampicin resistance, tNGS could be used for the rapid detection of additional drug resistance including newer and repurposed drugs like Bedaquiline, Delamanid, Pretomanid, Linezolid and Clofazimine for which no rapid molecular tests are currently available. A variety of clinical samples can be used and there are wide choices available for DNA extraction. The targets for tNGS could be amplified using commercial kits or in house primers. tNGS could be performed using different platforms like Illumina, Oxford Nanopore Technology and/or Ion torrent and diverse bio-informatic pipeline options. Positioning of a tNGS with portability system in the current TB diagnostic algorithm and its use in the clinical management of patients’ needs further evaluation and efforts.
及时发现耐药性是全球结核病管理的先决条件。虽然通过液体或固体方法进行表型药敏试验(pDST)需要时间,但目前的基因型药敏试验可以直接从临床标本中进行,但仅针对有限数量的耐药变异。与需要培养的全基因组测序(WGS)相比,靶向下一代测序(tNGS)是一种快速、经济的方法,使用直接样品进行测序。tNGS提供全面的耐药分析,如果直接从临床样本进行,周转时间为3-4天。对于具有利福平耐药的呼吸道样本,tNGS可用于快速检测其他耐药性,包括较新的和重新使用的药物,如贝达喹啉、Delamanid、Pretomanid、利奈唑胺和氯法齐明,目前尚无快速分子检测方法。可以使用各种临床样本,并且有广泛的选择可用于DNA提取。tNGS的靶标可以使用商业试剂盒或内部引物进行扩增。tNGS可以使用不同的平台进行,如Illumina, Oxford Nanopore Technology和/或Ion torrent以及各种生物信息管道选项。tNGS便携系统在当前结核病诊断算法中的定位及其在患者临床管理中的应用需要进一步的评估和努力。
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引用次数: 0
Effectiveness of FDA vital staining in follow UP of DR PTB patients on longer treatment regimen under NTEP FDA 生命体征染色法在跟进接受国家非传染性疾病防治计划较长疗程治疗的肺结核病人方面的成效
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2024.04.011
Aswathy S A , Anuj K. Bhatnagar , M. Hanif

Background

This high prevalent time of drug resistant tuberculosis need early finding of patients who are failing the longer treatment regimen, which can be done by using a simple method rather than using liquid culture which is expensive, consuming more time and technology.

Methods

Prospective observational study of 116 diagnosed cases of DR PTB patients attending at RBIPMT hospital, from December 2020 to December 2021. After primary analysis patients were followed up at end of first six months of treatment to give 2 sputum samples for examination by both culture and FDA staining at Intermediate Reference Laboratory, Delhi.

Results

Of 116 patients 57 were male and 59 were female, maximum in their 2nd to 4th decade of life. In all 6 months follow up, the relationship between the results of culture and FDA staining was found to be significant. After the end of 2nd month the diagnostic accuracy of FDA was almost 100%. Overall sensitivity of FDA staining was 79.25%, specificity was 98.87%, with diagnostic accuracy 97.08%.

Conclusions

FDA staining was found to be as effective as liquid culture in the follow up of drug resistant pulmonary tuberculosis patients on longer treatment regimen and will help not only in reducing the burden of DRTB in India but also saving the resources.
耐药结核病的高流行时间要求对长期治疗方案失败的患者进行早期发现,这可以通过使用一种简单的方法而不是使用昂贵、耗时和技术的液体培养来完成。方法对2020年12月至2021年12月在RBIPMT医院就诊的116例确诊的DR PTB患者进行前瞻性观察研究。初步分析后,在治疗前六个月结束时对患者进行随访,并在德里中间参比实验室提供2份痰样本进行培养和FDA染色检查。结果116例患者中,男性57例,女性59例,以2 ~ 4 10岁最多。在所有6个月的随访中,发现培养结果与FDA染色之间的关系显著。2个月后,FDA的诊断准确率接近100%。FDA染色的总体敏感性为79.25%,特异性为98.87%,诊断准确率为97.08%。结论fda染色法与液体培养法在耐药肺结核患者长期治疗随访中具有同等效果,不仅有助于减轻印度耐药结核病患者的负担,而且有助于节约资源。
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引用次数: 0
Evaluation of active case finding for Tuberculosis in selected districts of Madhya Pradesh, India (2023-24): Challenges and opportunities 对印度中央邦选定地区结核病活跃病例发现情况的评估(2023- 2024年):挑战与机遇
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.06.002
Manju Toppo , Devendra Gour , Sharath Burugina Nagaraja , Bhavesh Modi , Jiwan Meena , Rama Singodiya Lodha , Madhav Bansal , Shailendra Kumar Patne , Seema Badkur , Khushali Solanki , Gursharan Singh Mehta , Rashmi Pilkhwal , Nilufar Mondal , Khushboo Gupta , Paramjeet Singh Mewara , Deepanshu Pawar

Introduction

Tuberculosis (TB) remains a major public health concern in India, necessitating proactive strategies such as Active Case Finding (ACF) to improve case detection among high-risk populations. This study evaluates ACF implementation in seven districts of Madhya Pradesh, assessing key performance indicators and identifying challenges encountered by program implementers.

Methods

A mixed-methods study was conducted from August 2023 to January 2024, integrating quantitative analysis of ACF performance indicators with qualitative insights from key stakeholders. The study assessed mapping, screening, presumptive TB case identification, testing, diagnosis, and treatment initiation rates. In-depth interviews were conducted with District Tuberculosis Officers (DTOs), Medical Officers (MOTCs), District Program Coordinators (DPCs), and field staff to explore implementation challenges. Data were analyzed using Epi-Info 7, and thematic analysis was applied to qualitative findings.

Results

None of the districts met all six ACF quality indicators. Only six districts met the mapping target (≥11 %), while none achieved the screening target (>90 %). Presumptive TB case identification was below 5 % in all districts, and testing rates varied between 75 and 94.9 %. While two districts exceeded the diagnostic threshold (>5 %), others performed sub-optimally. Treatment initiation was successful (>95 %) in five districts. Key challenges included inadequate mapping, workforce constraints, TB-related stigma, and inconsistent diagnostic practices.

Conclusion

ACF implementation in Madhya Pradesh demonstrated critical gaps, particularly in early case detection and community engagement. Strengthening workforce training, community awareness, and diagnostic infrastructure is essential to improve ACF outcomes and achieve India's TB elimination goals by 2025.
在印度,结核病(TB)仍然是一个主要的公共卫生问题,需要采取主动病例发现(ACF)等主动战略,以改善高危人群的病例发现。本研究评估了ACF在中央邦七个地区的实施情况,评估了关键绩效指标,并确定了项目执行者遇到的挑战。方法于2023年8月至2024年1月进行了一项混合方法研究,将ACF绩效指标的定量分析与关键利益相关者的定性见解相结合。该研究评估了制图、筛查、推定结核病例识别、检测、诊断和治疗起始率。与地区防治结核病官员(dto)、医务官员(motc)、地区规划协调员(dpc)和实地工作人员进行了深入访谈,以探讨实施方面的挑战。使用Epi-Info 7对数据进行分析,并对定性结果进行专题分析。结果6个区县均未达到ACF的全部6项质量指标。只有6个地区达到了测绘目标(≥11%),而没有一个地区达到筛查目标(> 90%)。所有地区的推定结核病例识别率低于5%,检测率在75%至94.9%之间变化。虽然两个地区超过了诊断阈值(5%),但其他地区表现不佳。在5个区,开始治疗是成功的(95%)。主要挑战包括不充分的地图绘制、人力限制、结核病相关的污名以及不一致的诊断做法。结论:中央邦acf的实施存在重大差距,特别是在早期病例发现和社区参与方面。加强劳动力培训、社区意识和诊断基础设施对于改善ACF成果和实现印度到2025年消除结核病的目标至关重要。
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引用次数: 0
Mutation analysis of the latency-associated gene Rv2660c in Mycobacterium tuberculosis clinical isolates from South Sulawesi, Indonesia: In-silico prediction of implications for antigenicity 印度尼西亚南苏拉威西结核分枝杆菌临床分离株潜伏期相关基因Rv2660c的突变分析:对抗原性影响的计算机预测
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.04.009
Sadiya Ramli , Nihayatul Karimah , Astutiati Nurhasanah , Najdah Hidayah , Muhammad Nasrum Massi , Doddy Irawan Setyo Utomo , Rizalinda Sjahril , Fadhilah Syamsuri , Irda Handayani

Background

The Rv2660c gene, associated with Mycobacterium tuberculosis (Mtb) latency and survival, is considered highly conserved. However, genetic variations may influence pathogenicity and drug resistance. This study investigates mutations in the Rv2660c gene and their potential impact on protein structure and function.

Materials and Methods

The Rv2660c gene from 40 clinical isolates was analysed using PCR amplification and sequencing. Structural and immunological analyses were conducted using I-TASSER, B-cell epitope prediction tools, T-cell epitope prediction, and molecular docking simulations to evaluate the effects of mutations on protein structure and immune interactions.

Results

A T>C mutation at position 139 was identified in one isolate (MDR094R, NCBI GenBank Accession PV544294), resulting in a phenylalanine-to-leucine substitution at position 47 (Phe47Leu). This variation was also found in several other strains, M. tuberculosis strain SEA14117P6C4 (CP.041797.1.), M. tuberculosis strain 24 (CP136191.1), and M. tuberculosis strain 4 (CP136200.1). Phylogenetic analysis showed that proteins with the Phe47Leu mutation formed a separate cluster, indicating a unique evolutionary trajectory. Structural predictions indicated minimal changes in the protein structure, with slight alterations near the mutation site. Immunological analysis revealed that the mutation affected both continuous and discontinuous B-cell epitopes, altering their conformation and length. T-cell epitope predictions showed reduced binding affinity for certain HLA alleles, while some epitopes gained higher affinity. Docking studies confirmed minor changes in binding energy and hydrogen bond interactions.

Conclusion

The Phe47Leu mutation in the Rv2660c gene underscores the genetic diversity of M. tuberculosis and may influence antigenicity and immune recognition. These findings highlight the importance of further functional validation to assess the implications of this variation, particularly in the context of vaccine design and host-pathogen interactions.
Rv2660c基因与结核分枝杆菌(Mtb)的潜伏期和存活相关,被认为是高度保守的。然而,遗传变异可能影响致病性和耐药性。本研究探讨了Rv2660c基因突变及其对蛋白质结构和功能的潜在影响。材料与方法对40例临床分离株Rv2660c基因进行PCR扩增和测序分析。使用I-TASSER、b细胞表位预测工具、t细胞表位预测和分子对接模拟进行结构和免疫学分析,以评估突变对蛋白质结构和免疫相互作用的影响。结果在一个分离株(MDR094R, NCBI GenBank登录PV544294)中鉴定出139位点的sa T>;C突变,导致47位点(Phe47Leu)出现苯丙氨酸-亮氨酸取代。在结核分枝杆菌SEA14117P6C4 (CP.041797.1.)、结核分枝杆菌24 (CP136191.1)和结核分枝杆菌4 (CP136200.1)中也发现了这种变异。系统发育分析表明,携带Phe47Leu突变的蛋白形成了一个单独的簇,表明了一个独特的进化轨迹。结构预测显示蛋白质结构的微小变化,在突变位点附近有轻微的改变。免疫学分析显示,突变影响了连续和不连续的b细胞表位,改变了它们的构象和长度。t细胞表位预测显示对某些HLA等位基因的结合亲和力降低,而一些表位获得了更高的亲和力。对接研究证实了结合能和氢键相互作用的微小变化。结论Rv2660c基因的Phe47Leu突变凸显了结核分枝杆菌的遗传多样性,并可能影响其抗原性和免疫识别。这些发现强调了进一步功能验证以评估这种变异的意义的重要性,特别是在疫苗设计和宿主-病原体相互作用的背景下。
{"title":"Mutation analysis of the latency-associated gene Rv2660c in Mycobacterium tuberculosis clinical isolates from South Sulawesi, Indonesia: In-silico prediction of implications for antigenicity","authors":"Sadiya Ramli ,&nbsp;Nihayatul Karimah ,&nbsp;Astutiati Nurhasanah ,&nbsp;Najdah Hidayah ,&nbsp;Muhammad Nasrum Massi ,&nbsp;Doddy Irawan Setyo Utomo ,&nbsp;Rizalinda Sjahril ,&nbsp;Fadhilah Syamsuri ,&nbsp;Irda Handayani","doi":"10.1016/j.ijtb.2025.04.009","DOIUrl":"10.1016/j.ijtb.2025.04.009","url":null,"abstract":"<div><h3>Background</h3><div>The Rv2660c gene, associated with <span><span>Mycobacterium tuberculosis</span></span><span> (Mtb) latency and survival, is considered highly conserved. However, genetic variations may influence pathogenicity and drug resistance. This study investigates mutations in the Rv2660c gene and their potential impact on protein structure and function.</span></div></div><div><h3>Materials and Methods</h3><div>The Rv2660c gene from 40 clinical isolates was analysed using PCR<span> amplification and sequencing. Structural and immunological analyses were conducted using I-TASSER, B-cell epitope prediction tools, T-cell epitope prediction, and molecular docking simulations to evaluate the effects of mutations on protein structure and immune interactions.</span></div></div><div><h3>Results</h3><div>A T&gt;C mutation at position 139 was identified in one isolate (MDR094R, NCBI GenBank Accession PV544294), resulting in a phenylalanine-to-leucine substitution at position 47 (Phe47Leu). This variation was also found in several other strains, <em>M. tuberculosis</em> strain SEA14117P6C4 (CP.041797.1.), <em>M. tuberculosis</em> strain 24 (CP136191.1), and <em>M. tuberculosis</em><span><span> strain 4 (CP136200.1). Phylogenetic analysis showed that proteins with the Phe47Leu mutation formed a separate cluster, indicating a unique evolutionary trajectory. Structural predictions indicated minimal changes in the protein structure, with slight alterations near the mutation site. Immunological analysis revealed that the mutation affected both continuous and discontinuous B-cell epitopes, altering their conformation and length. T-cell epitope predictions showed reduced </span>binding affinity<span> for certain HLA alleles, while some epitopes gained higher affinity. Docking studies confirmed minor changes in binding energy and hydrogen bond interactions.</span></span></div></div><div><h3>Conclusion</h3><div><span>The Phe47Leu mutation in the Rv2660c gene underscores the genetic diversity of </span><em>M. tuberculosis</em><span> and may influence antigenicity<span> and immune recognition. These findings highlight the importance of further functional validation to assess the implications of this variation, particularly in the context of vaccine design and host-pathogen interactions.</span></span></div></div>","PeriodicalId":39346,"journal":{"name":"Indian Journal of Tuberculosis","volume":"72 ","pages":"Pages S60-S71"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
“Comparative study of gastric aspirate and bronchoalveolar lavage smear with CBNAAT examination for diagnosis of pulmonary tuberculosis in sputum smear negative suspected patients” 《痰涂片阴性疑似肺结核患者胃吸液及支气管肺泡灌洗涂片与CBNAAT检查诊断肺结核的比较研究》
Q3 Medicine Pub Date : 2025-12-01 DOI: 10.1016/j.ijtb.2025.04.002
Abhi D. Mukharya , Madhavi L. Dhameliya , Jigna B. Dave , Priya P. Mehta

Introduction

Pulmonary tuberculosis (TB) continues to pose a significant global health challenge, particularly in low- and middle-income countries (LMICs), where the burden of the disease is highest. Despite advances in medical science, accurate diagnosis of TB remains problematic, especially in patients with negative sputum smear results.

Aims and objectives

This study aims to compare the efficacy of gastric aspirate and bronchoalveolar lavage (BAL) smear examinations to that of the Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) for the diagnosis of pulmonary TB in patients who are sputum smear-negative.

Methods

This prospective observational study was conducted in the Respiratory Medicine department of Sir T Hospital Bhavnagar. The study included sputum smear-negative patients aged 18 years and older who had high clinical and radiological suspicion of pulmonary TB. Gastric aspirate and BAL samples were collected from these patients and analyzed using AFB smear microscopy and CBNAAT. Data were collected over 1.5 years, and the diagnostic yields of the different methods were compared to determine the most effective approach.

Results

The study included 54 participants (24 females and 30 males) aged 20–79 years. The majority of participants exhibited prolonged productive coughs, low-grade fever, weight loss, and loss of appetite. Gastric aspirate AFB smear results were 98.1 % negative and 1.9 % positive, while CBNAAT results showed 88.9 % with no Mtb detected and 11.1 % with Mtb detected without Rifampicin resistance. For BAL, AFB smear results were 94.4 % negative and 5.6 % positive, and CBNAAT results showed 63.0 % with no Mtb detected, 35.2 % with Mtb detected without Rifampicin resistance, and 1.9 % with Mtb detected with Rifampicin resistance.

Conclusion

The findings indicate that BAL CBNAAT has a higher diagnostic yield compared to gastric aspirate methods in sputum smear-negative patients. Combining CBNAAT with traditional smear methods enhances the accuracy and timeliness of TB diagnosis, leading to more effective treatment initiation. These results suggest that integrating CBNAAT into routine diagnostic protocols could significantly improve TB management, especially in resource-limited settings. Further research is recommended to optimize these diagnostic approaches for broader application.
肺结核(TB)继续构成重大的全球卫生挑战,特别是在该疾病负担最重的低收入和中等收入国家。尽管医学取得了进步,但对结核病的准确诊断仍然存在问题,特别是对痰涂片结果为阴性的患者。目的和目的本研究旨在比较胃吸痰和支气管肺泡灌洗(BAL)涂片检查与基于墨盒的核酸扩增试验(CBNAAT)在痰涂片阴性患者中诊断肺结核的疗效。方法本前瞻性观察研究在巴夫纳格尔爵士T医院呼吸内科进行。该研究包括18岁及以上的痰涂片阴性患者,他们在临床和放射学上有肺结核的高度怀疑。收集这些患者的胃吸液和BAL样本,并使用AFB涂片显微镜和CBNAAT进行分析。数据收集超过1.5年,并比较不同方法的诊断率,以确定最有效的方法。结果54名参与者(24名女性,30名男性),年龄20-79岁。大多数参与者表现出长时间的咳嗽、低烧、体重减轻和食欲不振。胃吸液AFB涂片阴性98.1%,阳性1.9%,而CBNAAT涂片未检出Mtb的占88.9%,未检出Mtb的占11.1%,未检出利福平耐药。AFB涂片阴性94.4%,阳性5.6%;CBNAAT涂片未检出Mtb的占63.0%,未检出耐利福平的占35.2%,检出耐利福平的占1.9%。结论BAL CBNAAT对痰涂片阴性患者的诊断率高于胃吸痰法。将CBNAAT与传统涂片方法相结合,可提高结核病诊断的准确性和及时性,从而更有效地开始治疗。这些结果表明,将CBNAAT纳入常规诊断方案可以显著改善结核病管理,特别是在资源有限的环境中。建议进一步研究以优化这些诊断方法以获得更广泛的应用。
{"title":"“Comparative study of gastric aspirate and bronchoalveolar lavage smear with CBNAAT examination for diagnosis of pulmonary tuberculosis in sputum smear negative suspected patients”","authors":"Abhi D. Mukharya ,&nbsp;Madhavi L. Dhameliya ,&nbsp;Jigna B. Dave ,&nbsp;Priya P. Mehta","doi":"10.1016/j.ijtb.2025.04.002","DOIUrl":"10.1016/j.ijtb.2025.04.002","url":null,"abstract":"<div><h3>Introduction</h3><div><span>Pulmonary tuberculosis (TB) continues to pose a significant global health challenge, particularly in low- and middle-income countries (LMICs), where the burden of the disease is highest. Despite advances in medical science, accurate diagnosis of TB remains problematic, especially in patients with negative </span>sputum smear results.</div></div><div><h3>Aims and objectives</h3><div><span>This study aims to compare the efficacy of gastric aspirate and </span>bronchoalveolar lavage<span> (BAL) smear examinations to that of the Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) for the diagnosis of pulmonary TB in patients who are sputum smear-negative.</span></div></div><div><h3>Methods</h3><div>This prospective observational study was conducted in the Respiratory Medicine<span> department of Sir T Hospital Bhavnagar. The study included sputum smear-negative patients aged 18 years and older who had high clinical and radiological suspicion of pulmonary TB. Gastric aspirate and BAL samples were collected from these patients and analyzed using AFB smear microscopy and CBNAAT. Data were collected over 1.5 years, and the diagnostic yields of the different methods were compared to determine the most effective approach.</span></div></div><div><h3>Results</h3><div><span>The study included 54 participants (24 females and 30 males) aged 20–79 years. The majority of participants exhibited prolonged productive coughs, low-grade fever, weight loss, and loss of appetite<span>. Gastric aspirate AFB smear results were 98.1 % negative and 1.9 % positive, while CBNAAT results showed 88.9 % with no Mtb detected and 11.1 % with Mtb detected without </span></span>Rifampicin resistance. For BAL, AFB smear results were 94.4 % negative and 5.6 % positive, and CBNAAT results showed 63.0 % with no Mtb detected, 35.2 % with Mtb detected without Rifampicin resistance, and 1.9 % with Mtb detected with Rifampicin resistance.</div></div><div><h3>Conclusion</h3><div>The findings indicate that BAL CBNAAT has a higher diagnostic yield compared to gastric aspirate methods in sputum smear-negative patients. Combining CBNAAT with traditional smear methods enhances the accuracy and timeliness of TB diagnosis, leading to more effective treatment initiation. These results suggest that integrating CBNAAT into routine diagnostic protocols could significantly improve TB management, especially in resource-limited settings. Further research is recommended to optimize these diagnostic approaches for broader application.</div></div>","PeriodicalId":39346,"journal":{"name":"Indian Journal of Tuberculosis","volume":"72 ","pages":"Pages S56-S59"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Indian Journal of Tuberculosis
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