Pouzol Stephane, Khaja Mafij Uddin Mohammad, Islam Ashabul, Jabin Maha Sultana, Nigou Jérôme, Banu Sayera, Hoffmann Jonathan
Medical and Scientific Department, Merieux Foundation, Lyon, France
Infectious Disease Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Dhaka District, Bangladesh.
BMJ Open. 2024 Sep 16;14(9):e087026. doi: 10.1136/bmjopen-2024-087026.
The WHO estimates a gap of about 30% between the incident (10.6 million) and notified (7.5 million) cases of tuberculosis (TB). Combined with the growing recognition in prevalence surveys of the high proportion of cases identified who are asymptomatic or paucisymptomatic, these data underscore how current symptom screening approaches and use of diagnostic tests with suboptimal performance on sputum miss large numbers of cases. Thus, the development of sputum-free biomarker-based tests for diagnosis is becoming necessary, which the WHO has already identified as a priority for new TB diagnostics.The objective of this study is to evaluate a combination of exhaled breath condensate (EBC) samples and mycobacterial lipoarabinomannan (LAM) as point-of-care (POC) assays to identify TB patients.
This prospective diagnostic accuracy study is conducted at the TB Screening and Treatment Centre of International Center for Diarrhoeal Disease Research, Bangladesh, on a cohort of adults and adolescents >11 years of age. A total of 614 individuals with presumptive pulmonary TB based on TB signs, symptoms and radiography are being recruited from 28 August 2023. Spot sputum is collected for standard reference testing (L-J culture, GeneXpert MTB/Rif, acid-fast Bacilli microscopy) to fine-tune categorisation of TB disease status for each participant, defined as (1) definite TB (at least one positive standard reference test); (2) probable TB (not microbiologically confirmed but under TB treatment); (3) possible TB (no TB treatment but signs, symptoms and radiography suggestive of TB); (4) other respiratory disease (microbiologically not confirmed and no radiography presenting abnormalities compatible with TB); and (5) unknown (no microbiological evidence with normal/no TB abnormalities with radiography). Urine and EBC specimens will be subjected to LAM POC testing and biobanked for further investigation. Statistical analyses will include an assessment of diagnostic accuracy by constructing receiver operating curves and calculating sensitivity and specificity, as well as post-test probabilities.
The study protocol was approved by the Research Review Committee as well as the Ethical Review Committee of icddr,b and recorded under a protocol reference number, PR-2301. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings, and shared with national and international policymaking bodies.
世界卫生组织估计，结核病（TB）的发病病例数（1060万）与报告病例数（750万）之间存在约30%的差距。此外，患病率调查越来越多地认识到，无症状或症状轻微的病例占比很高，这些数据凸显了当前症状筛查方法以及对痰液检测性能欠佳的诊断测试会遗漏大量病例。因此，开发无需痰液的基于生物标志物的诊断测试变得很有必要，世界卫生组织已将其确定为新型结核病诊断方法的优先事项。本研究的目的是评估呼出气冷凝液（EBC）样本和分枝杆菌脂阿拉伯甘露聚糖（LAM）作为即时检测（POC）方法来识别结核病患者的效果。
这项前瞻性诊断准确性研究在孟加拉国腹泻病研究国际中心的结核病筛查与治疗中心对11岁以上的成人和青少年队列进行。自2023年8月28日起，共招募614名基于结核病体征、症状和影像学检查疑似患有肺结核的个体。采集即时痰液用于标准参考检测（L-J培养、GeneXpert MTB/Rif、抗酸杆菌显微镜检查），以微调每位参与者的结核病疾病状态分类，定义为：（1）确诊结核病（至少一项标准参考检测呈阳性）；（2）疑似结核病（未经微生物学确诊但正在接受结核病治疗）；（3）可能患有结核病（未接受结核病治疗但体征、症状和影像学检查提示患有结核病）；（4）其他呼吸道疾病（未经微生物学确诊且影像学检查未呈现与结核病相符的异常）；（5）未知（无微生物学证据且影像学检查正常/无结核病异常）。尿液和EBC样本将接受LAM即时检测并储存用于进一步研究。统计分析将包括通过构建受试者工作曲线、计算敏感性和特异性以及检测后概率来评估诊断准确性。
该研究方案已获得研究审查委员会以及icddr,b的伦理审查委员会批准，并记录在方案参考编号PR-2301下。研究结果将提交给开放获取的同行评审期刊，在学术会议上展示，并与国家和国际决策机构分享。
