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Cited by 154Infectious Diseases and TuberculosisTuberculosis Research and EpidemiologyBacterial Infections and Vaccines

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

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Donovan, Joseph, Thu, Do Dang Anh, Phu, Nguyen Hoan, Dung, Vu Thi Mong, Quang, Tran Phu, Nghia, Ho Dang Trung, Oanh, Pham Kieu Nguyet, Nhu, Tran Bao +8 more·2020·The Lancet Infectious Diseases
DOI 10.1016/s1473-3099(19)30649-8PMC PMC7045088
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Abstract

BACKGROUND: Xpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. METHODS: In this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3-4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status. FINDINGS: Between Oct 16, 2017, and Feb 10, 2019, 205 patients were randomly assigned to Xpert Ultra (n=103) or Xpert (n=102). The sensitivities of Xpert Ultra and Xpert for tuberculous meningitis diagnosis against a reference standard of definite, probable, and possible tuberculous meningitis were 47·2% (95% CI 34·4-60·3; 25 of 53 patients) for Xpert Ultra and 39·6% (27·6-53·1; 21 of 53) for Xpert (p=0·56); specificities were 100·0% (95% CI 92·0-100·0; 44 of 44) and 100·0% (92·6-100·0; 48 of 48), respectively. In HIV-negative patients, the sensitivity of Xpert Ultra was 38·9% (24·8-55·1; 14 of 36) versus 22·9% (12·1-39·0; eight of 35) by Xpert (p=0·23). In HIV co-infected patients, the sensitivities were 64·3% (38·8-83·7; nine of 14) for Xpert Ultra and 76·9% (49·7-91·8; ten of 13) for Xpert (p=0·77). Negative predictive values were 61·1% (49·6-71·5) for Xpert Ultra and 60·0% (49·0-70·0) for Xpert. Against a reference standard of mycobacterial culture, sensitivities were 90·9% (72·2-97·5; 20 of 22 patients) for Xpert Ultra and 81·8% (61·5-92·7; 18 of 22) for Xpert (p=0·66); specificities were 93·9% (85·4-97·6; 62 of 66) and 96·9% (89·5-91·2; 63 of 65), respectively. Six (22%) of 27 patients had a positive test by Xpert Ultra after 4 weeks of treatment versus two (9%) of 22 patients by Xpert. INTERPRETATION: Xpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required. FUNDING: Wellcome Trust and the Foundation for Innovative New Diagnostics.

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  • Donovan 2020 found zero positive Xpert Ultra results in CSF from more than 100 participants with nontuberculous meningitis and in any participant with a confirmed diagnosis of nontuberculous meningitis.

    “Donovan 2020 assessed Xpert Ultra specificity in CSF from more than 100 participants with nontuberculous meningitis and found zero positive Xpert Ultra results in those with a probable or possible diagnosis of tuberculous meningitis and in any participant with a confirmed diagnosis of nontuberculous meningitis.”

    From Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults (2021) · cites this paper as Donovan 2020

    The Discussion states that no Xpert Ultra positives occurred among patients with probable or possible tuberculous meningitis or with a confirmed non-tuberculous meningitis diagnosis. But Table 1 in the Results lists 96 participants classified as not having tuberculous meningitis, only 48 of whom were assigned to Xpert Ultra—not more than 100 participants with non-tuberculous meningitis tested by Ultra. Page numbers were not available in our copy. (LLM, conf=0.91)

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Authors
Donovan, J., Thu, D. D. A., Phu, N. H., Dung, V. T. M., Quang, T. P., Nghia, H. D. T., Oanh, P. K. N., Nhu, T. B., Chau, N. V. V., Ha, V. T. N., Hang, V. T. T., Trinh, D. H. K., Geskus, R. B., Tan, L. V., Thuong, N. T. T., & Thwaites, G. E.
Affiliations
  • University of Oxford (GB)
  • Oxford University Clinical Research Unit (VN)
  • Hospital for Tropical Diseases (VN)
Corresponding author
Donovan, Joseph
ORCID
Venue
The Lancet Infectious Diseases
Publisher
Elsevier BV
Published
2020-03
Volume
20
Issue
3
Pages
299-307
ISSN
1473-3099 (ISSN-L)
DOI
10.1016/s1473-3099(19)30649-8
PMC
PMC7045088
OpenAlex
W3000453407
Cited by
154
References
21
Citations by year
2026: 15 · 2025: 18 · 2024: 28 · 2023: 29 · 2022: 18 · 2021: 23 · 2020: 23
FWCI
21.23
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Infectious Diseases (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Greater South Information System
Funders
Wellcome Trust (204904/Z/16/Z, 106680/B/14/Z)
Topics
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
tuberculous meningitis, Xpert MTB/RIF Ultra, Xpert MTB/RIF, diagnostic accuracy, cerebrospinal fluid, HIV coinfection, rifampicin resistance, Mycobacterium tuberculosis, molecular diagnosis, sensitivity and specificity, Vietnam, treatment response monitoring
MeSH terms
Humans, Predictive Value of Tests, Prospective Studies, Random Allocation, Sensitivity and Specificity, Tuberculosis, Meningeal, Vietnam, HIV Infections, Tuberculosis, Multidrug-Resistant, Molecular Diagnostic Techniques

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