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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2025-04-01
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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. |
| format | Article |
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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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