Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid

Abstract 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 y...

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Main Authors: S. M. Mazidur Rahman, Rumana Nasrin, Senjuti Kabir, Faisal Kabir, Asif Md. Rezaur Rahman, Mohammad Khaja Mafij Uddin, A. S. M. Iftekhairul Islam, Razia Khatun, Shakil Ahmed, Md. Badrul Alam Mondal, Mohammad Sadekur Rahman Sarkar, Sayeeda Anwar, Javeed A. Shah, Sayera Banu
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97664-2
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author S. M. Mazidur Rahman
Rumana Nasrin
Senjuti Kabir
Faisal Kabir
Asif Md. Rezaur Rahman
Mohammad Khaja Mafij Uddin
A. S. M. Iftekhairul Islam
Razia Khatun
Shakil Ahmed
Md. Badrul Alam Mondal
Mohammad Sadekur Rahman Sarkar
Sayeeda Anwar
Javeed A. Shah
Sayera Banu
author_facet S. M. Mazidur Rahman
Rumana Nasrin
Senjuti Kabir
Faisal Kabir
Asif Md. Rezaur Rahman
Mohammad Khaja Mafij Uddin
A. S. M. Iftekhairul Islam
Razia Khatun
Shakil Ahmed
Md. Badrul Alam Mondal
Mohammad Sadekur Rahman Sarkar
Sayeeda Anwar
Javeed A. Shah
Sayera Banu
author_sort S. M. Mazidur Rahman
collection DOAJ
description Abstract 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.
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spelling doaj-art-cf8945ce7e004a0dbfef4893ef72f12e2025-08-20T02:17:53ZengNature PortfolioScientific Reports2045-23222025-04-0115111010.1038/s41598-025-97664-2Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluidS. M. Mazidur Rahman0Rumana Nasrin1Senjuti Kabir2Faisal Kabir3Asif Md. Rezaur Rahman4Mohammad Khaja Mafij Uddin5A. S. M. Iftekhairul Islam6Razia Khatun7Shakil Ahmed8Md. Badrul Alam Mondal9Mohammad Sadekur Rahman Sarkar10Sayeeda Anwar11Javeed A. Shah12Sayera Banu13Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Department of Paediatrics, Shaheed Suhrawardy Medical College and HospitalDepartment of Neurology, National Institute of Neurosciences and HospitalDepartment of Neurology, National Institute of Neurosciences and HospitalDepartment of Paediatrics, Dhaka Medical College and HospitalDivision of Allergy and Infectious Diseases, Department of Medicine, University of WashingtonInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)Abstract 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.https://doi.org/10.1038/s41598-025-97664-2Tuberculous meningitisCerebrospinal fluidXpert MTB/RIF ultraXpert MTB/RIFDiagnosisChildren
spellingShingle S. M. Mazidur Rahman
Rumana Nasrin
Senjuti Kabir
Faisal Kabir
Asif Md. Rezaur Rahman
Mohammad Khaja Mafij Uddin
A. S. M. Iftekhairul Islam
Razia Khatun
Shakil Ahmed
Md. Badrul Alam Mondal
Mohammad Sadekur Rahman Sarkar
Sayeeda Anwar
Javeed A. Shah
Sayera Banu
Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
Scientific Reports
Tuberculous meningitis
Cerebrospinal fluid
Xpert MTB/RIF ultra
Xpert MTB/RIF
Diagnosis
Children
title Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
title_full Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
title_fullStr Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
title_full_unstemmed Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
title_short Performance of Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
title_sort performance of xpert mtb rif ultra for the diagnosis of tuberculous meningitis in children using cerebrospinal fluid
topic Tuberculous meningitis
Cerebrospinal fluid
Xpert MTB/RIF ultra
Xpert MTB/RIF
Diagnosis
Children
url https://doi.org/10.1038/s41598-025-97664-2
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