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Comorbidity profiles among sputum-positive tuberculosis patients in Cameroon. 喀麦隆痰液阳性肺结核患者的合并症概况。
Pub Date : 2024-10-02 DOI: 10.3389/ftubr.2024.1433856
Chefor Magha, Lucy Cho Nchang, Michael Weldeslassie, Desmond Akumtoh Nkimbeng, Nancielle Mbiatong Tchatat, Henry Dilonga Meriki, Kebede Deribe, Frank Noel Nietcho, Juluis Visnel Foyet, Fanny Fri Fombad, Tatiana Djikeussi Katcho, Jerome Fru Cho, Eyoab Iyasu Gebremeskel, Simon J Waddell, Kidist Bobosha, Melanie J Newport, Achim Hoerauf, Manuel Ritter, Samuel Wanji

Introduction: Comorbid non-communicable diseases (NCDs) like diabetes, cardiovascular diseases (CVD), kidney diseases, and hypertension, could have implications for tuberculosis (TB) treatment management and increase the disease burden amongst active TB patients.

Methods: This cross-sectional study aimed at profiling comorbidities amongst sputum-positive TB patients in the South West and Littoral regions of Cameroon and was relevant for improving disease management and public health interventions. Diabetes was defined by elevated blood glucose, body mass index (underweight: <18.5 kg/m2, normal: 18.5-<25.0 kg/m2, overweight: 25-<30 kg/m2 and obese: ≥30.0 kg/m2) and hypertension by elevated blood pressure levels (i.e., systolic ≥130 mmHg or diastolic ≥80 mmHg). Socio-demographic and clinical data were collected using case report forms. Descriptive analysis was performed, bivariate logistic regression analysis was computed with at least one comorbidity as the dependent variable (global model) and a multivariable logistic regression analysis was done to provide adjusted odds ratios (final model). The covariate with the highest p-value was removed until p < 0.25 cut-off, using R software version 4.3.1. p-value <0.05 at 95% confidence interval was considered statistically significant.

Results: Five hundred and forty-nine sputum-positive microscopically confirmed active TB patients were enrolled into this study. Two-thirds (65.8%) of the total patients were male. Overall, 56 sputum-positive TB patients had at least one non-communicable disease, thus a prevalence of 10.2% (95% CI = 7.9-13.0). The most frequently recorded NCD was diabetes 4.4% (95% CI = 3.1-6.7) followed by kidney disease 2% (95% CI = 1.1-3.6), hypertension 0.9% (95% CI = 0.4-2.2), and CVD 0.91% (95% CI = 0.4-2.2). Three TB patients (0.6%) had all four comorbidities examined. Age group (p < 0.001), and level of education (p = 0.049) were factors significantly associated with having at least one comorbidity.

Discussion: Our findings showed that diabetes was significantly the most prevalent comorbid NCD amongst sputum-positive TB patients (p < 0.001). HIV status, occupation, body mass index (BMI), and alcohol intake were not significantly associated with having at least one comorbidity. Implementing public health intervention programmes such as systematic screening of TB patients for NCDs especially diabetes is highly recommended for better control of these diseases.

导言:糖尿病、心血管疾病(CVD)、肾脏疾病和高血压等非传染性疾病(NCDs)的合并症可能会对结核病(TB)治疗管理产生影响,并加重活动性肺结核患者的疾病负担:这项横断面研究旨在分析喀麦隆西南部和滨海地区痰液呈阳性的肺结核患者的合并症,以改善疾病管理和公共卫生干预。糖尿病的定义是血糖升高、体重指数(体重不足:2、正常:18.5-2、超重:25-2 和肥胖:≥30.0 kg/m2)和高血压的定义是血压水平升高(即收缩压≥130 mmHg 或舒张压≥80 mmHg)。使用病例报告表收集社会人口学和临床数据。进行了描述性分析,以至少一种合并症为因变量计算了双变量逻辑回归分析(总体模型),并进行了多变量逻辑回归分析以提供调整后的几率比(最终模型)。使用 4.3.1 版 R 软件,剔除 p 值最高的协变量,直到 p < 0.25 临界值:这项研究共纳入了 549 名经显微镜确诊为痰液阳性的活动性肺结核患者。三分之二(65.8%)的患者为男性。总体而言,56 名痰液阳性肺结核患者至少患有一种非传染性疾病,患病率为 10.2%(95% CI = 7.9-13.0)。最常见的非传染性疾病是糖尿病 4.4% (95% CI = 3.1-6.7),其次是肾病 2% (95% CI = 1.1-3.6)、高血压 0.9% (95% CI = 0.4-2.2) 和心血管疾病 0.91% (95% CI = 0.4-2.2)。有三名肺结核患者(0.6%)同时患有这四种并发症。年龄组(p < 0.001)和受教育程度(p = 0.049)是与至少一种合并症显著相关的因素:讨论:我们的研究结果表明,在痰液呈阳性的肺结核患者中,糖尿病是最常见的合并非传染性疾病(p < 0.001)。艾滋病毒感染状况、职业、体重指数(BMI)和酒精摄入量与是否患有至少一种合并症没有明显关系。为了更好地控制这些疾病,我们强烈建议实施公共卫生干预计划,如对结核病患者进行系统的非传染性疾病(尤其是糖尿病)筛查。
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引用次数: 0
A broader evaluation of vaccine-induced T cell immunity against tuberculosis 对疫苗诱导的结核病 T 细胞免疫进行更广泛的评估
Pub Date : 2024-07-19 DOI: 10.3389/ftubr.2024.1435344
P. Ogongo
Although Bacillus Calmette-Guérin (BCG) vaccine, the only licensed vaccine against tuberculosis (TB), is the most widely used vaccine worldwide, TB is the second leading global killer from a single infectious agent responsible for over one million deaths annually. With the increasing threat of the emergence of drug-resistant TB, there is intense research toward better and more efficacious vaccines against TB. Indeed, TB vaccine research has blossomed in recent years: demonstration of sterilizing immunity against Mycobacterium tuberculosis (Mtb) challenge in non-human primates, the potential benefit of BCG revaccination in humans, and a phase IIb vaccine with ~50% efficacy against developing active disease. Consequently, several vaccines are set to begin phase 3 trials in 2024, and new candidates have entered phase 1 including mRNA-based TB vaccines. However, despite the enthusiasm, there are no known correlates of protection against TB, the antigens that induce protective immunity are incompletely defined, and the overreliance on Th1 cytokine production as an “absolute” measure of protection is increasingly debatable. In this perspective, I highlight the recent milestones in TB Vaccine research and the remaining challenges and propose suggestions for future considerations.
尽管卡介苗(BCG)是唯一获得许可的结核病(TB)疫苗,也是全球使用最广泛的疫苗,但结核病仍是全球第二大单一传染源杀手,每年造成一百多万人死亡。随着耐药性结核病威胁的不断增加,人们正加紧研究更好、更有效的结核病疫苗。事实上,近年来结核病疫苗的研究已取得了长足的进步:非人灵长类对结核分枝杆菌(Mtb)挑战的灭菌免疫得到了证实,卡介苗重新接种对人类有潜在的益处,IIb 期疫苗对活动性疾病有约 50% 的预防效果。因此,有几种疫苗将于 2024 年开始 3 期试验,还有新的候选疫苗进入了 1 期试验,其中包括基于 mRNA 的结核病疫苗。然而,尽管热情高涨,却没有已知的结核病保护相关因素,诱导保护性免疫的抗原定义也不完整,过度依赖 Th1 细胞因子的产生作为 "绝对 "的保护措施也越来越值得商榷。在这一视角中,我将重点介绍结核病疫苗研究的最新里程碑和仍然存在的挑战,并就未来的考虑提出建议。
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引用次数: 0
Diverse interactions of Mycobacterium tuberculosis infection and of BCG vaccination with SARS-CoV-2 结核分枝杆菌感染和卡介苗接种与 SARS-CoV-2 的多种相互作用
Pub Date : 2024-04-23 DOI: 10.3389/ftubr.2024.1378068
P. Salgame, S. Pentakota, J. C. M. Malabad, P. Narasimhan, Sheetal Verma, S. Prakash Babu, Vartika Sharma, Sonali Sarkar, Marissa M. Alejandria, Jerrold Ellner
The COVID pandemic and tuberculosis (TB) endemicity is double trouble to much of the world. SARS-CoV-2 and Mycobacterium tuberculosis (Mtb), causative agents of COVID and TB, respectively, are both infectious respiratory pathogens involving close communities and individuals. Both pathogens can cause lung disease, involving unbalanced inflammatory cell immune responses that can lead to a syndemic impact. Moreover, dual infection is common in certain settings. In low- and middle- income countries, most individuals with SARS-CoV-2 infection or COVID-19, in fact, will have been exposed to or infected with Mtb and some will develop active TB. Here we review the literature examining the diverse interactions of M. tuberculosis infection and of BCG vaccination with SARS-CoV-2. We discuss areas in which contradictory results have been published and conclude that there are still several unresolved issues that warrant further study on the co-pathogenesis of SARS-CoV-2 and Mtb and BCG- mediated heterologous protection against COVID-19.
COVID 大流行和结核病(TB)流行给世界许多地方带来了双重麻烦。SARS-CoV-2 和结核分枝杆菌(Mtb)分别是 COVID 和结核病的病原体,它们都是呼吸道传染病病原体,涉及密切接触的社区和个人。这两种病原体都能引起肺部疾病,涉及不平衡的炎症细胞免疫反应,可导致综合症影响。此外,双重感染在某些情况下很常见。在中低收入国家,大多数感染 SARS-CoV-2 或 COVID-19 的人实际上都曾接触或感染过 Mtb,其中一些人会发展成活动性肺结核。在此,我们回顾了研究结核杆菌感染和卡介苗接种与 SARS-CoV-2 之间各种相互作用的文献。我们讨论了已发表的结果相互矛盾的领域,并得出结论:仍有几个问题尚未解决,需要进一步研究 SARS-CoV-2 和 Mtb 的共同发病机制以及卡介苗介导的针对 COVID-19 的异源保护作用。
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引用次数: 0
Case report: Congenital multidrug-resistant tuberculosis 病例报告:先天性耐多药结核病
Pub Date : 2024-04-09 DOI: 10.3389/ftubr.2024.1343217
Hongyi Zhang, Lu Xia, Peize Zhang
Congenital multidrug-resistant tuberculosis (MDR-TB) is a rare disease with high mortality. We report a case of a neonate girl with congenital MDR-TB. The infant's mother underwent in vitro fertilization–embryo transfer and did not show any symptoms prior to delivery. After the 14th day of life, the infant had a fever and worsening difficulty breathing despite antibiotic treatment. She was then confirmed to have congenital MDR-TB and received ventilation and anti-TB treatment. When the infant's TB was diagnosed, her mother was screened for TB and found to have MDR-TB, affecting both her lungs and reproductive system. They both recovered and were discharged from the hospital, with anti-TB treatment ongoing.
先天性耐多药结核病(MDR-TB)是一种死亡率很高的罕见疾病。我们报告了一例患有先天性耐多药结核病的新生女婴。婴儿的母亲接受了体外受精-胚胎移植手术,分娩前未出现任何症状。婴儿出生第 14 天后,尽管接受了抗生素治疗,但仍出现发烧和呼吸困难。随后,她被证实患有先天性耐药结核病,并接受了通气和抗结核治疗。婴儿的结核病确诊后,她的母亲也接受了结核病筛查,结果发现她患有耐多药结核病,肺部和生殖系统均受到影响。她们都康复出院,抗结核治疗仍在继续。
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引用次数: 0
Test and treat approach for tuberculosis infection amongst household contacts of drug-susceptible pulmonary tuberculosis, Mumbai, India. 在印度孟买,对与药物敏感肺结核患者有家庭接触的人进行结核病感染检测和治疗。
Pub Date : 2024-01-01 DOI: 10.3389/ftubr.2024.1454277
Daksha Shah, Sampada Bhide, Rajesh Deshmukh, Jonathan P Smith, Satish Kaiplyawar, Varsha Puri, Vijay Yeldandi, Anand Date, Melissa Nyendak, Christine S Ho, Patrick K Moonan

Background: Mumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known.

Methods: We conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB® Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease.

Results: Among 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT.

Conclusion: A test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation.

背景:孟买是世界上人口最稠密的地区之一,也是印度结核病(TB)流行的主要原因。对家庭接触者(HHC)中的结核病感染(TBI)进行检测和治疗是国家结核病预防性治疗(TPT)政策的一部分。然而,在实践中,使用干扰素-γ释放测定(IGRA)检测感染的情况很有限,孟买的 TBI 患病率也不清楚:我们对 2021 年 9 月至 12 月期间在印度孟买接触到微生物学确诊的、药物敏感性肺结核患者并被通知接受抗结核治疗的高危人群进行了横断面研究。社区现场工作人员进行家访,并为 5 岁及以上的 HHC 提供 IGRA(QuantiFERON-TB® Gold In-Tube Plus)检测。在排除活动性结核病的可能性后,IGRA 检测结果呈阳性的高危人群将被转介接受结核病治疗。对所有 HHC 进行至少 24 个月的监测,以确定其是否发展为活动性结核病:在接受检测的 502 名高危人群中,有 273 人(54%)的 IGRA 检测结果呈阳性。共有 254 人(93%)被归类为 TBI,符合接受 TPT 的条件,其中 215 人(85%)开始接受 TPT,194 人(90%)成功完成了 TPT。每个家庭的 TBI 比率差异很大。在 32% 的家庭中,所有高危人群(100%)的 IGRA 均呈阳性,在 64% 的家庭中,超过 50% 的高危人群受到感染。总共有 22 个高危人群(4%;22/558)被诊断出患有结核病;其中,5 个高危人群在随访期间被诊断出患有结核病,其中 3 个高危人群的 IGRA 呈阳性,在初筛时没有疾病迹象,但选择不进行结核病治疗:结论:针对高危人群的检测和治疗策略发现了很大一部分 TBI 和继发性肺结核病例。基于家庭的 IGRA 检测带来了高参与率、临床评估、TPT 启动以及更多继发性病例的早期诊断。以社区为重点的检测和治疗方法在这一人群中是可行的,可以考虑在更大范围内实施。
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引用次数: 0
Understanding the bacillary load and host interaction to design a point-of-care test to diagnose tuberculosis 了解细菌负荷和宿主相互作用,设计诊断结核病的即时检测
Pub Date : 2023-08-16 DOI: 10.3389/ftubr.2023.1243479
P. Cardona
Designing of a Point-of-care test to diagnose tuberculosis (TB) is not an easy task. This viewpoint stems from the dichotomous diagnostic approach, based on the bacillary load estimated in latent tuberculosis infection (LTBI), thanks to the isoniazid chemoprophylaxis strategy, as well as the importance of imaging to differentiate between LTBI and TB. It integrates the “TB spectrum” elucidated through positron emission tomography-computed tomography scan (PET-CT) to highlight the dynamic nature of TB lesions. Additionally, it emphasizes the relevance of animal models that support this perspective, including the drainage of bacilli through foamy macrophages, which aids in understanding LTBI and its chemoprophylaxis, and the significance of lung anatomy in TB induction. Especially the role of interlobular septa and the encapsulation process and its role in lung lobe predilection impact disease progression. Moreover, it acknowledges the gender bias in TB, as its incidence is significantly higher in men across various socioeconomic circumstances, suggesting an unidentified biological mechanism. For a comprehensive approach, the impact of stress and cortisol levels is suggested as a new parameter to be considered, given their association with poverty, and social inequity, and their tendency to be higher in men. All this information has to be contemplated when designing an accurate point-of-care test. The test should encompass the complexity of TB and necessarily integrate both bacillary and host response parameters. It also should cover the diagnosis of extrapulmonary TB, and pay attention to immunosuppressed and pediatric population.
设计一种诊断结核病的即时检测方法并不是一件容易的事。这一观点源于基于潜伏性结核感染(LTBI)中估计的细菌负荷的二分诊断方法,这要归功于异烟肼化学预防策略,以及影像学对区分LTBI和结核病的重要性。它整合了通过正电子发射断层扫描-计算机断层扫描(PET-CT)阐明的“结核谱”,以突出结核病变的动态性质。此外,它强调了支持这一观点的动物模型的相关性,包括通过泡沫巨噬细胞排出杆菌,这有助于理解LTBI及其化学预防作用,以及肺解剖在TB诱导中的意义。特别是小叶间隔的作用和包封过程及其在肺叶偏爱中的作用影响疾病的进展。此外,它承认结核病中的性别偏见,因为在各种社会经济环境中,男性的发病率明显更高,这表明一种未知的生物学机制。考虑到压力和皮质醇水平与贫穷和社会不平等的关系,以及它们在男性中往往更高,因此建议将压力和皮质醇水平的影响作为一个需要考虑的新参数。在设计准确的即时检测时,必须考虑到所有这些信息。该测试应包含结核病的复杂性,并必须整合细菌和宿主的反应参数。它还应涵盖肺外结核的诊断,并注意免疫抑制和儿科人群。
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引用次数: 0
Atg8ylation as a host-protective mechanism against Mycobacterium tuberculosis. Atg8酰化作为宿主对结核分枝杆菌的保护机制。
Pub Date : 2023-01-01 Epub Date: 2023-09-29 DOI: 10.3389/ftubr.2023.1275882
Vojo Deretic

Nearly two decades have passed since the first report on autophagy acting as a cell-autonomous defense against Mycobacterium tuberculosis. This helped usher a new area of research within the field of host-pathogen interactions and led to the recognition of autophagy as an immunological mechanism. Interest grew in the fundamental mechanisms of antimicrobial autophagy and in the prophylactic and therapeutic potential for tuberculosis. However, puzzling in vivo data have begun to emerge in murine models of M. tuberculosis infection. The control of infection in mice affirmed the effects of certain autophagy genes, specifically ATG5, but not of other ATGs. Recent studies with a more complete inactivation of ATG genes now show that multiple ATG genes are indeed necessary for protection against M. tuberculosis. These particular ATG genes are involved in the process of membrane atg8ylation. Atg8ylation in mammalian cells is a broad response to membrane stress, damage and remodeling of which canonical autophagy is one of the multiple downstream outputs. The current developments clarify the controversies and open new avenues for both fundamental and translational studies.

自首次报道自噬作为细胞自主防御结核分枝杆菌以来,近二十年过去了。这有助于在宿主-病原体相互作用领域开辟一个新的研究领域,并使人们认识到自噬是一种免疫机制。人们对抗菌自噬的基本机制以及结核病的预防和治疗潜力越来越感兴趣。然而,令人困惑的体内数据已经开始出现在结核分枝杆菌感染的小鼠模型中。对小鼠感染的控制证实了某些自噬基因的作用,特别是ATG5,但没有证实其他ATG的作用。最近对ATG基因更完全失活的研究表明,多个ATG基因对于预防结核分枝杆菌确实是必要的。这些特定的ATG基因参与膜atg8酰化的过程。哺乳动物细胞中的Atg8酰化是对膜应激、损伤和重塑的广泛反应,其中典型的自噬是多种下游输出之一。目前的发展澄清了争议,并为基础研究和翻译研究开辟了新的途径。
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引用次数: 0
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Frontiers in tuberculosis
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