Rahman S M Mazidur, Nasrin Rumana, Kabir Senjuti, Kabir Faisal, Rahman Asif Md Rezaur, Uddin Mohammad Khaja Mafij, Islam A S M Iftekhairul, Khatun Razia, Ahmed Shakil, Mondal Md Badrul Alam, Sarkar Mohammad Sadekur Rahman, Anwar Sayeeda, Shah Javeed A, Banu Sayera
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
Department of Paediatrics, Shaheed Suhrawardy Medical College and Hospital, Dhaka, 1207, Bangladesh.
Sci Rep. 2025 Apr 16;15(1):13060. doi: 10.1038/s41598-025-97664-2.
Rapid and reliable diagnostic tests for tuberculous meningitis (TBM) in children remain limited. This study evaluated the performance of Xpert MTB/RIF Ultra (Ultra), an improved version of Xpert MTB/RIF (Xpert), for detecting TBM in children using cerebrospinal fluid (CSF). Children (0-14 years) presumptive of TBM were enrolled prospectively from three tertiary level hospitals in Dhaka, Bangladesh, from December 2019 to January 2022. CSF was tested by Ultra, Xpert, Lowenstein-Jensen (L-J) culture, and acid-fast bacilli (AFB) microscopy. Diagnostic performance was assessed against clinical case definitions, composite microbiological reference standard (CMRS), and L-J culture. Of 187 children, Ultra detected TBM in 23.4% of cases, significantly higher than the 9.1% detected by Xpert (p < 0.001). Compared to the clinical case definition of probable and definite TBM, Ultra exhibited a sensitivity of 88% (44/50), markedly outperforming Xpert (34%, 17/50) and L-J culture (30%, 15/50) (p < 0.001). Against the CMRS, Ultra's sensitivity was 100% (44/44), compared to Xpert (38.6%, 17/44) and L-J culture (34.1%, 15/44) (p < 0.001). AFB microscopy showed very low sensitivity (2.3%, 1/44). Negative predictive values for both clinical case definition and CMRS were higher for Ultra (95.8-100%) than Xpert (80.6-84.1%) and L-J culture (79.7-83.1%) (p < 0.001). Compared to gold standard L-J culture, Ultra's sensitivity (100%, 15/15) was also higher than Xpert (93.3%, 14/15) (p = 0.316), with specificities of 83.1% (143/172) and 98.3% (169/172), respectively. Ultra detected 26 TBM cases missed by other tests, with most (84.6%) in the 'trace detected' category. Due to the high performance, Ultra can be used widely at health care settings of high TB burden countries like Bangladesh for rapid and accurate diagnosis of paediatric TBM using CSF samples.
用于儿童结核性脑膜炎（TBM）的快速可靠诊断测试仍然有限。本研究评估了Xpert MTB/RIF Ultra（Ultra）这一Xpert MTB/RIF（Xpert）的改进版本，使用脑脊液（CSF）检测儿童TBM的性能。2019年12月至2022年1月期间，前瞻性纳入了来自孟加拉国达卡三家三级医院疑似患有TBM的儿童（0至14岁）。通过Ultra、Xpert、罗氏培养基（L-J）培养和抗酸杆菌（AFB）显微镜检查对脑脊液进行检测。根据临床病例定义、综合微生物学参考标准（CMRS）和L-J培养评估诊断性能。在187名儿童中，Ultra检测出23.4%的病例患有TBM，显著高于Xpert检测出的9.1%（p < 0.001）。与可能和确诊TBM的临床病例定义相比，Ultra的敏感性为88%（44/50），明显优于Xpert（34%，17/50）和L-J培养（30%，15/50）（p < 0.001）。相对于CMRS，Ultra的敏感性为100%（44/44），而Xpert为38.6%（17/44），L-J培养为34.1%（15/44）（p < 0.001）。AFB显微镜检查显示敏感性非常低（2.3%，1/44）。Ultra对于临床病例定义和CMRS的阴性预测值（95.8 - 100%）高于Xpert（80.6 - 84.1%）和L-J培养（79.7 - 83.1%）（p < 0.001）。与金标准L-J培养相比，Ultra的敏感性（100%，15/15）也高于Xpert（93.3%，14/15）（p = 0.316），特异性分别为83.1%（143/172）和98.3%（169/172）。Ultra检测出其他测试遗漏的26例TBM病例，其中大多数（84.6%）属于“微量检测”类别。由于性能卓越，Ultra可在孟加拉国等高结核病负担国家的医疗机构中广泛用于使用脑脊液样本快速准确诊断儿童TBM。
